A TiO2/C catalyst having biomimetic channels and extremely low Pt loading for formaldehyde oxidation

This study presents a TiO₂/C hybrid material with biomimetic channels fabricated using a wood template. Repeated impregnations of pretreated wood chips in a Ti precursor were conducted, followed by calcination at 400–600 °C for 4 hours under a nitrogen atmosphere. The generated TiO₂ nanocrystals were homogenously distributed inside a porous carbon framework. With an extremely low Pt catalyst loading (0.04–0.1 wt%), the obtained porous catalyst could effectively oxidize formaldehyde to CO₂ and H₂O even under room temperature (conv. ∼100%). Wood acted as both a structural template and reduction agent for Pt catalyst generation in sintering. Therefore, no post H₂ reduction treatment for catalyst activation was required. The hierarchal channel structures, including 2–10 nm mesopores and 20 μm diameter channels, could be controlled by calcination temperature and atmosphere, which was confirmed by SEM and BET characterizations. Based on the abundant availability of wood templates and reduced cost for low Pt loading, this preparation method shows great potential for large-scale applications.

This study presents a TiO₂/C hybrid material with biomimetic channels fabricated using a wood template.

Formaldehyde (HCHO) is an important chemical feedstock that is widely used in the production of industrial resins, polymers and coating materials. However, formaldehyde is highly toxic and volatile, and it has been listed as a human carcinogen group I by the International Agency for Research on Cancer (IARC).¹ Formaldehyde is slowly emitted from building and furnishing materials, which can cause serious health problems. Developing an efficient and feasible catalyst for the removal of formaldehyde pollutant from indoor environment has received a growing concern recently.Inorganic porous materials are good candidates for application in the removal of formaldehyde either by physical absorption or chemical catalytic oxidation.^2,3 Inorganic porous materials have multi-shapes of pore structures and large surface areas, which allow formaldehyde molecules access into holes. Moreover, the inorganic framework of the material has high thermal stability, suggesting that the material can be thermally regenerated and reused for many times. Many inorganic porous material-based formaldehyde absorbents, such as active carbon,⁴ porous Al₂O₃ (ref. 5) and zeolite,⁶ have been investigated. For example, different porous Al₂O₃ materials were prepared by using the template method, which showed broad pore size distribution and good formaldehyde adsorption–desorption behavior.^7,8 However, the porous inorganic adsorbents have limited adsorption capacities, resulting in only a short effective time.Formaldehyde oxidation over porous material-supported catalysts is a promising technology because formaldehyde can be continuously oxidized to CO₂ and H₂O.^9–11 The porous structure can facilitate fast diffusion and mass transport of formaldehyde and products. Furthermore, the high surface area of the porous material provides a large number of active sites for formaldehyde adsorption and catalyst loading. Many catalyst-loaded porous materials or porous transition metal oxides were prepared and displayed excellent formaldehyde oxidation performance; some examples include Pt on ZSM-5 and NaY zeolites,^12,13 mesoporous Au, Pt or Pd/CeO₂,^14–16 VO_x/MCM,¹⁷ macro-mesoporous Pt/γ-Al₂O₃,¹⁸ Pd or Pt/TiO₂,^19–24 Pt/mesoporous ferrihydrite²⁵ and porous MnO₂.^26,27 Various organic templates were used in the preparation of TiO₂ with desired porosity, such as surfactants,^28,29 block copolymers^30–32 and even small organic molecules including salicylic acid and aspartic acid.³³ However, these organic templates generally have a high price, which hinders their potential for large-scale applications. Another issue is that the noble metal catalyst loading is still high (1–2.5%) to reach effective formaldehyde oxidation.Biomass materials have low cost and natural hierarchal structures in the range from millimeters to nanometers,³⁴ which can be used as natural templates for porous material fabrication. TiO₂ with a porous structure has been prepared by bio-templating of naturally grown biomass materials, such as wood and bamboo;^22,35 however, there is no reported example on the use of the material as a catalyst in reactions such as organic oxidation. Herein, we presented a wood templated TiO₂/C material having biomimetic channel structures. The obtained material was different from the supported catalysts or core–shell structure materials, in which the catalyst layers are only coated inside or outside the porous structure. Wood templated TiO₂/C exhibited a hybrid structure; this resulted in the generation of TiO₂ nanocrystals, which were homogenously distributed inside the porous carbon framework because the Ti precursor penetrated into wood tissues before catalyst sintering. With an extremely low loading of Pt, this type of hierarchal structured material showed highly effective formaldehyde oxidation behavior even under room temperature.     

Nano-Fe3O4@walnut shell/Cu(ii) as a highly effective environmentally friendly catalyst for the one-pot pseudo three-component synthesis of 1,3-oxazine derivatives under solvent-free conditions

Fe₃O₄@walnut shell/Cu(ii) as an eco-friendly bio-based magnetic nano-catalyst was prepared by adding CuCl₂ to Fe₃O₄@walnut shell in alkaline medium. A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines were synthesized by the one-pot pseudo three-component reaction of β-naphthol, formaldehyde and various amines using nano-Fe₃O₄@walnut shell/Cu(ii) at 60 °C under solvent-free conditions. The catalyst was removed from the reaction mixture by an external magnet and was reusable several times without any considerable loss of its activity. This protocol has several advantages such as excellent yields, short reaction times, clean and convenient procedure, easy work-up and use of an eco-friendly catalyst.

Fe₃O₄@walnut shell/Cu(ii) as an eco-friendly bio-based magnetic nano-catalyst was prepared by adding CuCl₂ to Fe₃O₄@walnut shell in alkaline medium.

Biopolymers, especially cellulose and its derivatives, have some unparalleled properties, which make them attractive alternatives for ordinary organic or inorganic supports for catalytic applications.¹ Cellulose is the most abundant natural material in the world and it can play an important role as a biocompatible, renewable resource and biodegradable polymer containing OH groups.² Walnut shell is a natural, cheap, and readily available source of cellulose. Fe₃O₄ nanoparticles are coated with various materials such as surfactants,³ polymers,^4,5 silica,⁶ cellulose⁷ and carbon⁸ to form core–shell structures. Magnetic nanoparticles as heterogeneous supports have many advantages such as high dispersion in reaction media and easy recovery by an external magnet.⁹ Cu(ii) as a safe and ecofriendly cation is a good Lewis acid and can activate the carbonyl group for nucleophilic addition reactions.¹⁰1,3-Oxazines moiety has gained great attention from many organic and pharmaceutical chemists due to their broad range of biological activities such as anticancer,¹¹ anti-bacterial,¹² anti-tumor¹³ and anti-Parkinson''s disease.¹⁴Owing to the biological importance of benzo-fused 1,3-oxazines, various methods have been developed for the synthesis of these compounds. Some shown protocols for the synthesis of various 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines via a Mannich type condensation between a 2-naphthol, formaldehyde and a primary amine were reported. This protocol has been catalyzed by KAl(SO₄)₂·12H₂O (alum),¹⁵ ZrOCl₂,¹⁶ polyethylene glycol (PEG),¹⁷ thiamine hydrochloride (VB₁)¹⁸ and CCl₃COOH.¹⁹ Other methods of synthesis of oxazines are aza-acetalizations of aromatic aldehydes with 2-(N-substituted aminomethyl) phenols in the presence of an acid as catalyst²⁰ and electrooxidative cyclization of hydroxyamino compounds.²¹However, some of these catalysts have limitations such as inefficient separation of the catalyst from reaction mixtures, unrecyclable and environmental limitations. Therefore, the development of green and clean methodology for the preparation of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine derivatives is still an interesting challenge.Herein, we wish to report the preparation of Fe₃O₄@nano-walnut shell/Cu(ii) as a new and bio-based magnetic nanocatalyst and its using for one-pot synthesis of 1,3-oxazine derivatives via condensation of β-naphthol, primary amine and formaldehyde.     

E–Z isomerization of 3-benzylidene-indolin-2-ones using a microfluidic photo-reactor

Here, we report controlled E–Z isomeric motion of the functionalized 3-benzylidene-indolin-2-ones under various solvents, temperature, light sources, and most importantly effective enhancement of light irradiance in microfluidic photoreactor conditions. Stabilization of the E–Z isomeric motion is failed in batch process, which might be due to the exponential decay of light intensity, variable irradiation, low mixing, low heat exchange, low photon flux etc. This photo-μ-flow light driven motion is further extended to the establishment of a photostationary state under solar light irradiation.

(E)-3-Benzylidene-indolin-2-ones were efficiently converted to their corresponding (Z) -isomers at low temperature in the presence of light.

Functionalized 3-benzylidene-indolin-2-ones are an important structural motif in organic chemistry and are embedded in many naturally occurring compounds.¹ They found wide applications in molecular-motors,² energy harvesting dyes,³ pharmaceutical chemistry (sunitinib, tenidap),⁴ protein kinase inhibitors,⁵ pesticides,⁶ flavors,⁷ and the fragrance industry.⁸ In the last few decades, numerous protocols have been developed for the synthesis of novel indolin-2-ones. For instance, palladium (Pd)-catalysed intramolecular hydroarylation of N-arylpropiolamides,⁹ Knoevenagel condensation of oxindole and aldehyde,¹⁰ two-step protocols such as Ni-catalyzed CO₂ insertion followed by coupling reaction,¹¹ Pd-catalysed C–H functionalization/intramolecular alkenylation,¹² Pd(0)/monophosphine-promoted ring–forming reaction of 2-(alkynyl)aryl isocyanates with organoboron compound, and others.¹³Knoevenagel condensation is one of the best methods for the preparation of 3-benzylidene-indolin-2-ones, but often it gives mixture of E/Z isomeric products. Otherwise, noble metal-catalysed protocols received enormous interest. However, the limited availability, high price, and toxicity of these metals diminished their usage in industrial applications. Therefore, several research groups have been engaged in search of an alternative greener and cleaner approach under metal-free conditions. To address the diastereoisomeric issue, Tacconi et al. reported a thermal (300–310 °C) isomerization reaction of 3-arylidene-1,3-dihydroindol-2-ones,¹⁴ which suffers from poor reaction efficiency and E/Z selectivity. Therefore, transformations controlling E/Z ratio of 3-benzylidene-indolin-2-ones remains a challenging task and highly desirable (Scheme 1).Open in a separate windowScheme 1Functionalized 3-benzylidene-indolin-2-ones and alkenes in bioactive compounds and the accessible methods.On the other hand, selective E/Z stereo-isomerization of alkenes has been well established using various methods in the presence of light stimuli,^15a cations,^15b halogens or elemental selenium,¹⁶ palladium-hydride catalyst,¹⁰ cobalt-catalyst,¹⁷ Ir-catalyst,¹⁸ organo-catalysts.¹⁹ Among these, light-induced photostationary E/Z stereoisomerization is very attractive, due to its close proximity towards the natural process. In recent years, several light-driven molecular motors (controlled motion at the molecular level), molecular propellers,²⁰ switches,²¹ brakes,²² turnstiles,²³ shuttles,²⁴ scissors,²⁵ elevators,²⁶ rotating modules,²⁷ muscles,²⁸ rotors,²⁹ ratchets,³⁰ and catalytic self-propelled objects have been developed.³¹ Further, equipment''s relying on molecular mechanics were rapidly developed, particularly in the area of health care.Till date, controlled photo-isomerization of functionalized 3-benzylidene-indolin-2-ones is one of the puzzling problems to the scientific community. Photochemical reactions in batch process have serious drawbacks with limited hot-spot zone due to inefficient light penetration with increasing light path distance through the absorbing media, and the situation becomes poorer when the reactor size increases.^32,33 In contrast, the capillary microreactor platform has emerged as an efficient the artificial tool with impressive advantages, such as excellent photon flux, uniform irradiation, compatibility with multi-step syntheses, excellent mass and heat transfer, which lead to significant decrease the reaction time with improved yield or selectivity over batch reactors.^33a,34 To address the aforementioned challenges, it is essential to develop a highly efficient photo-microchemical flow approach for the controlled isomerization of functionalized 3-benzylidene-indolin-2-ones in catalyst-free and an environment friendly manner.     

A top-down design for easy gram scale synthesis of melem nano rectangular prisms with improved surface area

An unprecedented top-down design for the preparation of melem by 1 h stirring of melamine-based g-C₃N₄ in 80 °C concentrated sulfuric acid (95–98%) was discovered. The melem product was formed selectively as a monomer on the gram scale without the need for controlled conditions, inert atmosphere, and a special purification technique. The as-prepared air-stable melem showed a distinctive nano rectangular prism morphology that possesses a larger surface area than the melems achieved by traditional bottom-up designs making it a promising candidate for catalysis and adsorption processes.

A novel practical method for the gram scale preparation of melem possessing a nano rectangular prism morphology and improved specific surface area through a top-down depolymerization design was developed.

Triamino-s-heptazine or 2,5,8-triamino-tri-s-triazine known as “melem”, is a mysterious molecule and invaluable intermediate in the density of melamine rings to graphitic carbon nitride (g-C₃N₄) with a rigid heptazine structure with three pendant amino substituents.¹ Melem does not bear two of the strongest emission quenchers, namely C–H and O–H groups;² In this way it has unique optical properties³ and is known as an efficient metal-free luminescent material.⁴ High stability, the possibility for supramolecular self-assembly, tunable band gap, and an already rich physicochemical chemistry are some of the known properties for melem.^1b For this reason, melem has the potential to be used in photocatalysts, MOFs, COFs, electrochemistry sensors, flame retardants, TADF and related OLEDs, and liquid crystals.¹ The use of melem in solar hydrogen evolution⁵ and bioimaging⁶ is also known.Very few reports of its catalytic application are available, nevertheless, in recent years it has attracted much attention because of exploring its unique properties. Metal-free g-C₃N₄/melem hybrid photocatalysts have been used for visible-light-driven hydrogen evolution.⁷ Lei et al. used melem single crystal nanorods as a photocatalyst with modulated charge potentials and dynamics.⁸ Recently, Liu et al. improved the photocatalytic properties of carbon nitride for water splitting by attaching melem to Schiff base bonds.⁹ In another report, a promotion in photocatalytic activity was obtained by construction of melem/g-C₃N₄ vermiculite hybrid photocatalyst for photo-degradation of tetracycline.¹⁰ Lei et al. reported that H₂ evolution activity of melem derived g-C₃N₄ was 18 times higher than g-C₃N₄.¹¹ Melem was also utilized as a precursor for the preparation of rod-like g-C₃N₄/V₂O₅ heterostructure with enhanced sonophotocatalytic degradation for tetracycline antibiotics.¹² CO₂ cycloaddition into cyclic carbonates,¹³ non-sacrificial photocatalytic H₂O₂ production,³ water treatment,¹⁴ simultaneous reductions of Cr(vi) and degradation of 5-sulfosalicylic acid,¹⁵ are some of the catalytic applications of melem at various fields of sciences.The main protocol of preparing melem is the annealing of cyanamide, dicyanamide, or melamine, which requires precise temperature control under an inert atmosphere such as N₂ or argon. Just recently, the synthesis approaches for molecular s-heptazines as well as their applications and properties have been reviewed by Audebert et al.^1b Most of the reported methods do not lead to the preparation of pure monomer melem and are often mixed with its oligomers and polymerized derivatives,¹⁶ meanwhile the possibility of forming triazine oligomers or oligomers between melem and triazine cannot be precluded.^5,16c Complete polymerization of melamine at 500–550 °C leads to g-C₃N₄ and at 400–450 °C leads to melem-like derivatives,¹⁷ mostly a mixture of different products requiring careful attention during isolation and purification.⁵ Recently, Kessler and his colleague investigated the thermolysis of melamine, the formation of melem, and the formation of poly(triazine imide) from melem precursor via ionothermal as well as thermal condensation (conventional synthesis) as the back reaction of the melem condensation.¹⁸The growing demands for employing melem in new applications besides the serious problems in preparing pure samples necessitate the development of a simple and operational scale-up method that does not have any acute and controlled conditions.It is well-known that the polycondensation mode of g-C₃N₄ and consequently the chemical and thermal stability as well as texture properties strongly depend on the nitrogen rich precursors (cyanamide, dicyandiamide, urea, and melamine) as well as annealing temperature.¹⁹The interaction between the molecular precursors and/or intermediate compounds are critical factors.¹⁷ Due to some drawbacks associated with the g-C₃N₄ such as low electronic conductivity, a high rate of photogenerated electron–hole pairs, a low surface area, poor visible-light absorption, low quantum yield, and low solubility in almost all of the traditional solvents,²⁰ it has been subjected to various acid treatments, to promote its properties and photochemical activity.²¹ Various nanosheets with different properties and morphologies have been obtained depending on the precursor used, acid nature and concentration, as well as reaction temperature and time.²² However, the oxidation products such as cyameluric or cyanuric acids (Scheme 1) under high reaction temperatures and times have been reported.^21cOpen in a separate windowScheme 1The selective production of the monomer melem from melamine-based g-C₃N₄ presented in this work. Other molecules are possible decomposition and/or oxidation products of g-C₃N₄.Inspired by the previous reports to prepare the acidified g-C₃N₄, we started with melamine to synthesize the g-C₃N₄ by calcining at 550 °C under air,²³ followed by the treatment with H₂SO₄. Nevertheless, we discovered that stirring the melamine-based g-C₃N₄ at concentrated H₂SO₄ (95–98%) at 80 °C for a limited time (1 h), afforded selectively monomer melem in high yield (Scheme 1). Following the intercalation, chemical exfoliation, and protonation of nitrogen atoms of the g-C₃N₄ sheets at concentrated H₂SO₄,^22,24 the bridging C–NH–C groups between s-heptazine units breaks which releases the triamino-s-heptazine (melem) molecules as monomer (Scheme S1^†). Under these conditions the formation of oligomers was precluded because of the effective breaking of the bridging amino groups, however, the limited reaction time and moderate temperature prevented the tri-s-triazine ring-opening as well as the formation of the oxidation products such as cyameluric (or cyanuric) acids.^21c Thus, we developed a facile and easy gram-scale synthesis of melem from acidic depolymerization of melamine-based g-C₃N₄ with no need for controlled conditions, and inert atmosphere. The air-stable white powder was insoluble in most common solvents (H₂O, C₂H₅OH, CH₃OH, DMF, CH₃CN, acetone, etc.) and only dissolved in DMSO with a very limited solubility exactly like that reported for the isolated pure monomer melem.^5,25 A new and distinctive rectangular prism morphology with an improved surface area was detected for the as-prepared melem,^5,8,26 which makes our study even more unique and novel.^5,8,27 It is well known that both morphology and specific surface area play important roles in affecting the photocatalytic activity of semiconductors.^22,28 Thus, our study not only provides a novel practical method for the preparation of nanostructured monomer melem, but also paves a new pathway for increasing its surface area. The chemical structure and purity of the as-prepared melem were verified by the combination of different techniques including FT-IR, ¹H and ¹³C NMR, mass spectra, elemental analysis, XRD, XPS, DRS, and photoluminescence spectroscopy.FT-IR spectrum of g-C₃N₄ and the as-prepared melem are depicted in Fig. 1. While the peaks at 803 and 796 cm⁻¹ exhibited the vibrations of tri-s-triazine moieties in g-C₃N₄ and melem respectively, two intense bands at 1622 and 1471 cm⁻¹, consistent with those of monomer melem. The lack of obvious C–NH–C vibrations at around 1230 cm⁻¹ featured the absence or negligible amount of dimelem or further melem-oligomers in the product.^29a,5,8 In the region of NH-stretching frequencies, a spectrum characteristic of amides is observed: three diffuse absorption bands (3415, 3360, and 3106 cm⁻¹) indicate the presence of strong intermolecular hydrogen bonds and strong interaction between the amino-groups and the ring.^29a Inspection of the characteristic bands of melem presented in Fig. 1, no evidence for the formation of cyameluric acid or other oxidation products (Scheme 1) was detected.²⁹Open in a separate windowFig. 1FT-IR of the as-synthesized g-C₃N₄ and Melem.In the ¹³C NMR spectrum (Fig. S1^†), two signals at 165.8 and 156 ppm are assigned to carbon atoms adjacent to the amino groups and CN3 groups in heptazine rings, respectively.^1a,5 The ¹H NMR (Fig. S1^†) showed a sharp signal at 7.4 ppm assigned to six protons of the terminal amino groups of melem along with two weak broad signals at ∼8 ppm which can be attributed to the partial protonation of some nitrogens. The lack of the signal at 149.37 ppm in ¹³C NMR^29b and a high-field signal at ¹H NMR (10.9 ppm or higher)³⁰ strongly confirmed that our method precludes the formation of cyameluric acid accompanied by the desired melem.The mass spectrometry depicted in Fig. S2^† shows that the bulk material contains almost entirely monomer melem evidenced by the main peak at m/z 218 pertinent to a single unit of melem and a very little peak at m/z 419 corresponding to dimelem and nothing of higher mass.³¹ Also, no trace of the oxidation products was observed in mass spectra (m/z 129 and 221 for cyanuric and cyameluric acids, respectively).The C/N atomic ratio is one of the most significant clues to prove the successful formation of melem. The ratio of 0.605 found for the produced melem is very close to the theoretical value in the monomer melem (C/N = 0.6).^5,8A substantial evidence for the exclusive formation of monomer melem was achieved by the XRD pattern. Fig. 2 shows XRD patterns of melem and its polymeric graphitic carbon nitride used in this work. A great match with literature was observed.⁵ Two characteristic peaks of g-C₃N₄ at 2θ = 13.28° (100) and 27.47° (002) related to the in-plane structural packing motif, and interlayer-stacking of aromatic systems respectively, significantly changed after treatment with 80 °C concentrated sulfuric acid for 1 h and showed strong evidence for the formation of the monomer melem.^5,8 The former peak (100) became pronounced and shifted to a lower angle of 12.52°, while the latter one (002) was shortened in the melem and shifted to the higher angle of 2θ = 27.6° caused by decreased stacking distance between the melem inter-layers. More important is the emergence of a new intense peak at 6.16°, which is the unique characteristic of monomer melem,⁵ while, other weak peaks located at about 19, 23, 25, 29 and, 31 are almost looked at in the XRD patterns of both monomer and oligomers.^5,8 No trace of cyameluric acid as the possible oxidation product was detected in the XRD pattern of the resulting product.^21c,30Open in a separate windowFig. 2XRD patterns of g-C₃N₄ and the as-synthesized melem.Next, XPS was used to identify the chemical environments of the product as shown in Fig. 3 and S3.^† Only C, N, and trace amounts of O and S caused by the negligible remaining sulfuric acid and water can be detected (Fig. S3^†). The C1s signals (Fig. 3 left) can be fitted into five components with binding energies of 284.5 eV, 285.18 eV, 287.78 eV, 288.58 eV, and 293.58 eV. The C signal at 284.5 eV is exclusively assigned to carbon atoms (C–C bonding) in a pure carbon environment, such as graphitic or amorphous carbons.^26,32 The signals at 285.16 and 287.78–288.3 eV attributed to graphitic carbon sp² C–C, and the sp² trigonal C–N bonding (s-triazine ring), respectively, characteristic of melem structure.^8,33 The advent of a high-energy satellite at 293.7 eV corresponds to the Π-electron delocalization in the heptazine system of melem.²⁷ The N 1s signals (Fig. 3 right) were deconvolved into five peaks. The signals with binding energies of 398.4, 400, and 401–404 eV are associated with the sp²-hybridized nitrogen (C N–C), tertiary nitrogen (N–(C)₃), and protonated amino groups (C–N–H) in melem, respectively.^33a,34 The emergence of (N–(C)₃) undoubtedly indicated the preservation of tri-s-triazine units (C₆N₇, basic part of melem molecule) during treatment with 80 °C concentrated acid. Thus, no significant changes in the carbon nitride heterocycles such as the oxidation transformation of terminal C–NH–C to C–OH–C and/or tri-s-triazine ring-opening reactions occurred.^21c,36 The advent of a satellite at high binding energy of 406 eV corresponds to the partial protonation of some nitrogens (N–H⁺).³⁵Open in a separate windowFig. 3XPS spectra of the as-prepared melem, left: C 1s and right: N 1s.The morphology of the as-synthesized product was determined by FESEM (Fig. 4A). The FESEM images clearly show microsized rectangular prisms with thickness ranging from ∼50 to 350 nm, which was completely different with carbon nitride with the main nanosheets morphology.³⁷ To the best of our knowledge, this is the first report for such a morphology for melem,⁸ that aroused our curiosity to assess its surface properties. The porosity of the samples was determined by N₂ physisorption experiments. The N₂ adsorption/desorption isotherms and pore size distributions of the as-prepared melem are given in Fig. 4B. The sample exhibited typical type IV isotherms with H3 hysteresis loop according to the IUPAC classification,²⁷ suggesting mesoporous structures with slit-shaped pores resulting from the aggregation of plate-like particles.³⁸ The BET specific surface area of the as-synthesized melem was found to be 19.54 m² g⁻¹ which is about 3–4 folds larger than those reported for bulk melems as 5.63 m² g⁻¹,²⁷ and 7.02 m² g⁻¹,¹² as well as melem nanorods as 4.87 m² g⁻¹,⁸ obtained from the condensation of melamine. These results clearly show the superiority of our easy-to-make melem over the other samples obtained by the traditional bottom-up design under quite controlled conditions.^5,8,27 The mesoporous nature of the as-synthesized melem was further supported by the pore-size distribution analysis depicted as an inset of isotherm (in Fig. 4B) indicating an average diameter of pore size at 2.1 nm.Open in a separate windowFig. 4(A) FESEM image and (B) BET N₂ adsorption/desorption isotherms of the as-synthesized melem.The TG analysis of the as-synthesized melem exhibited three mass loss steps (Fig. S4^†). At the first step, the sample lost about 10% of its weight at less than 200 °C caused by removing water and ethanol molecules absorbed during the elution process. The second one was begun at around 240 °C and continued to 500 °C with the evolution of ammonia and small amounts of HCN, attributed to the condensation polymerization of the monomer.The third thermal decomposition was accelerated above 500 °C (with releasing HCN and C₂N₂),⁶ rendering strong evidence for the absence of triazine derivatives (or lower) in the as-prepared product and once again ruled out the tri-s-triazine ring-opening reactions during the synthesis of melem in this work.^21c,39 The high thermal stability of the produced melem,⁶ is comparable with the parent g-C₃N₄, making it more appropriate for comparative studies and applied goals that add further benefits to our sample.Lastly, the optical properties of the sample were evaluated using UV-Vis diffuse reflectance spectroscopy (DRS). As shown in Fig. S5,^† the absorption maximum wavelength of the resulting melem locates at 310 nm coincides with that reported in the literature.^5,40 The band edge of melem shifted to the lower wavelength (380 nm) compared to the polymer g-C₃N₄ (460 nm), caused by decreasing in Π-electron delocalization in the heptazine system of melem which stretches the band gap from 2.7 eV (polymer) to 3.45 eV (monomer melem) in excellent agreement with reported theoretical value for monomer melem (3.497 eV).^5,27 Further support for this claim was obtained by fluorescence spectra. Fig. 5 shows the comparative fluorescence spectra of the as-synthesized melem, under 355 nm light excitation. As shown in Fig. 5, it is found that the fluorescence emission of polymer g-C₃N₄ peaked at 476 nm,^40a shifted to 412 nm in the melem coincide with Ricci report (415 nm).⁴¹ In addition, the photoluminescence intensity of the resulting melem increased significantly compared to polymer g-C₃N₄ in broad agreement with literature indicating that the condensation of melem to g-C₃N₄ causes the weaker photoluminescence.^40aOpen in a separate windowFig. 5Photoluminescence spectra of g-C₃N₄ and the as-synthesized melem under 355 nm light excitation.Finally, our formulation is very simple and robust with respect to processing conditions to overcome the potential scale-up problems to make it operational and amenable to scalability readily. As an example, a 5 fold semi-scaled-up procedure using 1.0 g g-C₃N₄ led to the isolation of the related pure monomer melem in 95% yield within 1 h.In summary, we developed a novel operational protocol for easy gram scale preparation of air-stable monomer melem through a top-down synthesis design with no need for any control conditions and further purification. Our analyses ruled out the presence of the starting polymer as well as the formation of oligomers and oxidation products in the final product highlighting the selectivity of the method toward the monomer of melem. The distinctive nano rectangular prism morphology with desired surface area and thermal stability, as well as the appropriate photoluminescence property qualifies our synthesized melem for applied goals and makes it a promising alternative for catalysis and adsorption processes which is under investigation in our lab.     

Preparation of Ni-microsphere and Cu-MOF using aspartic acid as coordinating ligand and study of their catalytic properties in Stille and sulfoxidation reactions

In this study, the thermal and catalytic behavior of Ni-microsphere and Cu-MOF were investigated with aspartic acid as the coordinating ligand with different morphologies. The Ni-microsphere and Cu-MOF with aspartic acid, as the coordinating ligand, were prepared via a solvothermal method. The morphology and porosity of the obtained Ni microsphere and Cu-MOF were characterized by XRD, FTIR, TGA, DSC, BET and SEM techniques. The catalytic activity of the Ni-microsphere and Cu-MOF was examined in Stille and sulfoxidation reactions. The Ni microsphere and Cu-MOF were easily isolated from the reaction mixtures by simple filtration and then recycled four times without any reduction of catalytic efficiency.

In this study, the thermal and catalytic behavior of Ni-microsphere and Cu-MOF were investigated with aspartic acid as the coordinating ligand with different morphologies.

Cross-coupling reaction is one of the most significant methods to create carbon–carbon bonds in organic synthesis. There are many approaches, including, Suzuki, Stille, and Sonogashira cross-coupling reactions, which are well recognized and highly applicable in organic synthesis. Among them, the Stille reaction, which is an increasingly versatile tool for the formation of carbon–carbon bonds, involves the coupling of aryl halides with organotin reagents.¹ However, these reactions generally require expensive transition metal catalysts such as Pd.² Therefore, it is necessary to develop a new economic, green, and efficient methodology to reduce the environmental impact of the reaction. They are also important intermediates in organic chemistry and have been widely used as ligands in catalysis. The direct oxidation of sulfides is an important method in organic chemistry. Besides, they are also valuable synthetic intermediates for the construction of chemically and biologically important molecules, which usually synthesized by transition metal complexes.³ In this regard, different transition metal complexes of mercury(ii) oxide/iodine,⁴ oxo(salen) chromium(v),⁵ rhenium(v) oxo,⁶ H₅IO₆/FeCl₃,⁷ Na₂WO₄/C₆H₅PO₃H₂,⁸ chlorites and bromites,⁹ NBS¹⁰etc. have been introduced as catalysts. However, these catalysts have several drawbacks; including, separation problems from the reaction medium, harsh reaction conditions, and generating a lot of waste. In order to solve these drawbacks, of separation and isolation of expensive homogeneous catalysts is the heterogenization of homogeneous catalysts and generation of a new heterogeneous catalytic system. Metal–organic frameworks (MOFs) are a class of porous crystalline materials, which show great advantages, i.e. their enormous structural and chemical diversity in terms of high surface area,^11,12 pore volumes,¹³ high thermal,¹⁴ and chemical stabilities,¹⁵ various pore dimensions/topologies, and capabilities to be designed and modified after preparation.¹⁶ In this sense, it is worth mentioning that these features would result in viewing these solids as suitable heterogeneous catalysts for organic transformations.^17–22 MOFs materials are prepared using metal ions (or clusters) and organic ligands in solutions (i.e. solvothermal or hydrothermal synthesis). MOF structures are affected by metal and organic ligands, leading to have more than 20 000 different MOFs with the largest pore aperture (98 Å) and lowest density (0.13 g cm⁻³).²³ Generally, surface area and pore properties of MOFs seem quite dependent on their metal and ligand type as well as synthesis conditions and the applied post-synthesis modifications. The largest surface area was measured in Al-MOF (1323.67 m² g⁻¹)^24,25 followed by ZIF-8-MOF (1039.09 m² g⁻¹),²⁶ while the lowest value was with Zn-MOF (0.86 m² g⁻¹),²⁷ followed by γ-CD-MOF (1.18 m² g⁻¹)²⁸ and Fe₃O(BDC)₃ (7.6 m² g⁻¹).²⁹ Microspheres are either microcapsule or monolithic particles, with diameters in the range (typically from 1 μm to 1000 μm),²⁹ depending on the encapsulation of active drug moieties. In this regard, there are two types of microspheres: microcapsules, defined, as spherical particles in the size range of about 50 nm to 2 mm and micro matrices.³⁰ Microsphere structures have recently attracted much attention due to their unique properties, such as large surface area,³¹ which make them suitable for tissue regenerative medicine,³²i.e. as cell culture scaffolds,³³ drug-controlled release carriers³⁴ and heterogeneous catalysis.³⁵ Many chemical synthetic methods has been developed for their synthesis, including seed swelling,³⁶ hydrothermal or solvothermal methods,³⁶ polymerization,³⁷ spray drying³⁸ and phase separation.³⁹ Among these methods, the solvothermal synthesis has been used as the most suitable methodology to prepare a variety of nanostructural materials, such as wire, rod,⁴⁰ fiber,⁴¹ mof⁴² and microsphere.⁴³ In this sense, the synthesis process involves the use of a solvent under unusual conditions of high pressure and high temperature.⁴⁴ The properties of microspheres are highly dependent on the number of pores, pore diameter and structure of pore.⁴⁵ The degree of porosity depends on various factors such as temperature, pH, stirring speed, type, and concentration of porogen, polymer, and its concentration.⁴⁶ There have been numerous studies to investigate the coordination behavior of a ligand with different metals under the same conditions.^47–49 Herein, we aim at comparing the catalytic behavior of Ni-microsphere and Cu-MOF with aspartic acid as the coordinating ligand in Stille and sulfoxidation reactions (Scheme 1).Open in a separate windowScheme 1(a) Schematic synthesis of Ni microsphere and Cu-MOF and their application as catalyst (b) topological structure of Cu-MOF (c) topological of Ni microsphere.     

Synthesis of novel benzopyran-connected pyrimidine and pyrazole derivatives via a green method using Cu(ii)-tyrosinase enzyme catalyst as potential larvicidal,antifeedant activities

A series of benzopyran-connected pyrimidine (1a–g) and benzopyran-connected pyrazole (2a–i) derivatives were synthesized via Biginelli reaction using a green chemistry approach. Cu(ii)-tyrosinase was used as a catalyst in the synthesis of compounds 1a–g and 2a–ivia the Biginelli reaction. The as-synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy, and elemental analysis. The as-synthesized compounds were screened for larvicidal and antifeedant activities. The larvicidal activity was evaluated using the mosquito species Culex quinquefasciatus, and the antifeedant activity was evaluated using the fishes of Oreochromis mossambicus. The compounds 2a–i demonstrated lethal effects, killing 50% of second instar mosquito larvae when their LD₅₀ values were 44.17, 34.96, 45.29, 45.28, 75.96, and 28.99 μg mL⁻¹, respectively. Molecular docking studies were used for analysis based on the binding ability of an odorant binding protein (OBP) of Culex quinquefasciatus with compound 2h (binding energy = −6.12 kcal mol⁻¹) and compound 1g (binding energy = −5.79 kcal mol⁻¹). Therefore, the proposed target compounds were synthesized via a green method using Cu(ii)-enzyme as a catalyst to give high yield (94%). In biological screening, benzopyran-connected pyrazole (2h) was highly active compared with benzopyran-connected pyrimidine (1a–g) series in terms of larivicidal activity.

Cu(ii)-tyrosinase catalytic help with the synthesis of benzopyran-connected pyrimidine and pyrazole derivatives and their larvicidal activity.

Benzopyrans (coumarins) are an important group of naturally occurring compounds widely distributed in the plant kingdom and have been produced synthetically for many years for commercial uses.¹ In addition, these core compounds are used as fragrant additives in food and cosmetics.² The commercial applications of coumarins include dispersed fluorescent brightening agents and as dyes for tuning lasers.³ Some important biologically active natural benzopyran (coumarin) derivatives are shown in Fig. 1. Mosquitoes are the vectors for a large number of human pathogens compared to other groups of arthropods.⁴ Their uncontrollable breeding poses a serious threat to the modern humanity. Every year, more than 500 million people are severely affected by malaria. The mosquito larvicide is an insecticide that is specially targeted against the larval life stage of a mosquito. Particularly, the compound bergapten (Fig. 1), which shows the standard of larivicidal activity,⁵ is commercially available, and it was used as a control in this study for larvicidal screening. Moreover, the antifeedant screening defense mechanism makes it a potential candidate for the development of eco-friendly ichthyocides. Coumarin derivatives exhibit a remarkably broad spectrum of biological activities, including antibacterial,^6,7 antifungal,^8–10 anticoagulant,¹¹ anti-inflammatory,¹² antitumor,^13,14 and anti-HIV.¹⁵Open in a separate windowFig. 1Biologically active natural benzopyran compound.Coumarin and its derivatives can be synthesized by various methods, which include the Perkin,¹⁶ Knoevenagel,¹⁷ Wittig,¹⁸ Pechmann,¹⁹ and Reformatsky reactions.Among these reactions, the Pechmann reaction is the most widely used method for the preparation of substituted coumarins since it proceeds from very simple starting materials and gives good yields of variously substituted coumarins. For example, coumarins can be prepared by using various reagents, such as H₂SO₄, POCl₃,²⁰ AlCl₃,²¹ cation exchange resins, trifluoroacetic acid,²² montmorillonite clay,²³ solid acid catalysts,²⁴ W/ZrO₂ solid acid catalyst,²⁵ chloroaluminate ionic liquid,²⁶ and Nafion-H catalyst.²⁷Keeping the above literature observations, coumarin derivatives 1a–g and 2a–i are usually prepared with the conventional method involving CuCl₂·2H₂O catalysis with using HCl additive. This reduces the yield and also increases the reaction time. To overcome this drawback, we used mushroom tyrosinase as a catalyst without any additive, a reaction condition not reported previously. The as-synthesized compounds were used for the biological screening of larvicidal and antifeedant activities (marine fish). In addition, in this study, we considered the molecular docking studies study based on previous studies for performing the binding ability of hydroxy-2-methyl-4H-pyran-4-one (the root extract of Senecio laetus Edgew) with the odorant binding protein (OBP) of Culex quinquefasciatus.²⁸     

Yield stress fluids and fundamental particle statistics

Yield stress in complex fluids is described by resorting to fundamental statistical mechanics for clusters with different particle occupancy numbers. Probability distribution functions are determined for canonical ensembles of volumes displaced at the incipient motion in three representative states (single, double, and multiple occupancies). The statistical average points out an effective solid fraction by which the yield stress behavior is satisfactorily described in a number of aqueous (Si₃N₄, Ca₃(PO₄)₂, ZrO₂, and TiO₂) and non-aqueous (Al₂O₃/decalin and MWCNT/PC) disperse systems. Interestingly, the only two model coefficients (maximum packing fraction and stiffness parameter) turn out to be correlated with the relevant suspension quantities. The latter relates linearly with (Young’s and bulk) mechanical moduli, whereas the former, once represented versus the Hamaker constant of two particles in a medium, returns a good linear extrapolation of the packing fraction for the simple cubic cell, here recovered within a relative error ≈ 1.3%.

Yield stress in complex fluids is described by resorting to fundamental statistical mechanics for clusters with different particle occupancy numbers.

Yield stress fluids form a particular state of matter,¹ displaying non-linear and novel visco-plasto-elastic flow dynamics upon different boundary conditions. As their name says, they don’t flow until a certain load, the so-called yield stress (or point, τ₀), is applied. This value may be generally interpreted as a shear stress threshold for the breakage of interparticle connectivity.² Furthermore, as it initiates motion in the system, it is connected to mechanical inertia³ and particle settling, i.e. it is a terse summary of buoyancy, dynamic pressure, weight, viscous and yield stress resistances.⁴ For prototype systems such as colloids dispersed in a liquid, yield points sensibly depend on the mechanism by which the solid phase tends to interact or aggregate.^5–8 The macroscopic constitutive equations they obey, such as the Herschel–Bulkley model, were shown to correspond, over a four-decade range of shear rates, to the local rheological response.⁹From the side of an experimenter, however, unambiguously defining a yield stress may not always be straightforward. It can be affected by the experimental procedure adopted, always considering a measurement or some extrapolation technique with the limit of zero shear. Conversely, unyielded domains may be defined by areas where the shear stress second invariant falls below the yield value, plus some small semi-heuristic constant.¹⁰ In addition, theoretically, the meaning of notions like τ₀ and rheological yielding were questioned to be only qualitative or even to stand for an apparent quantity.¹¹ The dependence they generally show on timescales characteristic of the applied (mechanical) disturbance, also suggested an intimate relationship¹² between yield stress and dispersion thixotropy.¹³ On the other hand, assigning a hydrodynamic or mechanical state below the yield point to a material that is not flowing seems not to be scientifically sound. Experimental values are normally obtained by extrapolation of limited data, whereas careful measurements below the yield point would actually imply that flow takes place.¹⁴At any rate, the analysis of properly defined τ₀ concepts forms the subject of interesting investigations and is still a powerful tool in many applications, including macromolecular suspensions,¹⁵ gels, colloidal gels and organogels,^16–18 foams, emulsions and soft glassy materials.¹⁹ It allows for effective comparisons between the resistances which fluids initially oppose to the shear perturbation, somehow specifying a measure of the particle aggregation states taking place in a given dispersant. Electrorheological materials, for instance, exhibit a transition from liquid-like to solid-like behaviors, which is often examined by a yield stress investigation upon a given fluid model (e.g. the Bingham model or the Casson model).^20,21 The combination of yield stress measurements with AFM techniques can be used to well-characterize the nature of weak particle attractions and surface forces at nN scales.⁸ Further issues of a more geometrical nature, which naturally connect to τ₀, are rheological percolation²² and its differences from other connectivity phenomena, such as the onset of electric²³ or elastic percolation.^24,25 In granular fluids, it relates with the theory of jammed states,²⁶ originally pioneered by Edwards.²⁷In nanoscience as well, the stability control and characterization in single and mixed dispersions or melts is an important and complex step.^28,29 Carbon nanotube suspensions,³⁰ for example, can be prepared in association with other molecular systems, like surfactants and polymers^31–33 or by (either covalent or non-covalent) functionalization of their walls with reactive groups, which increases the chemical affinity with dispersing agents.³⁴ As a consequence of large molecular aspect ratios and significant van der Waals’s attractions, the nanotube aggregation is highly enhanced, giving rise to strongly anisotropic systems of crystalline ropes and entangled network bundles, which are difficult to exfoliate, suspend or even characterize.³⁵ Stable CNT dispersions of controlled molecular mass may also exhibit polymeric behavior, and be quantitatively studied by equations taken from the well-established science of macromolecules.^36,37This paper puts forward a basic approach, mostly focused on equilibrium arguments, to devise a yield stress law connected with particle statistics. By conjecturing an ensemble of effective volumes ‘displaced’ at the incipient state of motion, a statistical mechanics picture of τ₀ is proposed. This affords a phenomenological hypothesis that can be developed with reasonable simplicity. The derived relations are applied to typical disperse systems in colloid science and soft matter, such as aqueous and nonaqueous suspensions of ceramic/metal oxides and nanoparticles.     

Synthesis of novel 1,2,4-thiadiazinane 1,1-dioxides via three component SuFEx type reaction

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors. The β-aminoethane sulfonamides were obtained through sequential Michael addition of amines to α,β-unsaturated ethenesulfonyl fluorides followed by further DBU mediated sulfur(vi) fluoride exchange (SuFEx) reaction with amines at the S–F bond.

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors.

The 1,2,4-thiadiazinane 1,1-dioxide motif can be found in many biologically active compounds for vastly different medical conditions. For example, verubecestat (1) has been in phase III clinical trials as a β-amyloid precursor protein cleaving enzyme (BACE 1) inhibitor to treat moderate and prodromal Alzheimer''s disease.¹ Ribizzi et al. have shown that taurolidine (2) displays cytotoxic activity against certain human tumour cells,² but primarily it is used as an antibacterial agent.³ In addition, benzothiadiazines (3) are patented as ATP-sensitive potassium channel modulators for the treatment of respiratory, central nervous, and endocrine system disorders.⁴ 1,2,4-Thiadiazinane 1,1-dioxides of this type may be formed by various methods;^5–13 most closely related to the present work is the [2 + 2 + 2] sulfa Staudinger cycloaddition of sulfonylchlorides and imines, in which case β-sultams may also be formed through the corresponding [2 + 2] cycloaddition.^14,15 α,β-Unsaturated sulfonyl fluorides 4 are so far rarely encountered as starting materials for organic synthesis.^16–18 The literature on this reagent describe it as a connector molecule,¹⁹ and a warhead in chemical biology.^20–22 There are only four publications that, so far, have reported the use of α,β-unsaturated sulfonyl fluoride based compounds as starting materials in organic synthesis.^23–26 Based on our earlier experience with the reactivity of aryl α,β-unsaturated sulfonyl fluoride towards various amine nucleophiles¹⁷ (Scheme 1), we hypothesized that an α,β-unsaturated sulfonyl fluoride of type 4 can possibly be explored for the synthesis of thiadiazinanes. This hypothesis was based on observation of low amounts of the six-membered product was formed along with the major β-sultam product 5 when p-nitrophenylethenesulfonyl fluoride was subjected to excess methyl amine in methylene chloride as a solvent and triethylamine as additional base at room temperature (Scheme 1).Open in a separate windowScheme 1Formation of 1,2,4-thiadiazinane 1,1-dioxides, along with β-sultams, when aryl ethenesulfonyl fluorides are subjected to large excess of primary amines in DCM as solvent and DBU as catalyst.The reactivity of dichloromethane (DCM) as a methylene donor was unfamiliar to us at the time, but a literature survey quickly revealed that organic solvents (DMF,²⁷ DMSO,^28–30 CHCl₃ (ref. 31 and 32) and CH₂Cl₂ (ref. 33 and 34)) have proved to be more than solvents. DCM has indeed been reported to act as a bis-electrophilic methylene donor in the presence of strong bases and nucleophiles³³ (e.g. carboxylic acids,³⁵ thiols,³⁶ amines, etc.). DCM may also form hydrochloride salts,³⁷ aminals,³⁸ and quaternary salts³⁹ when reacted with tertiary and secondary amines. These reactions were reviewed by Mills et al.⁴⁰ and the kinetics of the reaction of DCM with pyridine was documented by Rudine et al.⁴¹ Liu and co-workers reported formation of methylene-bridged 3,3′-bis-(oxazolidin-2-one) through reaction of oxazolidin-2-ones with DCM and sodium hydride.⁴² Cui et al. reported the synthesis of bispidine with the utilisation of DCM as a C1 unit.⁴³ Dipyrrolidylmethane CH₂(pyr)₂ and dipiperidylmethane, CH₂(pip)₂ were synthesized via the condensation of the secondary amine precursors and DCM at room temperature in the absence of light.⁴⁴ Another reaction of amines with methylene chloride yielded aminals rapidly.⁴⁵ Matsumoto et al. reported the reaction of DCM with ketones or esters in the presence of secondary amines at high pressure whereby DCM was used as methylene bridge in forming both C–C and C–N bonds.⁴⁶ Zhang and co-workers also published the formation of simultaneous carbon–carbon bond and carbon-nitrogen bonds whereby DCM acted as a synthon in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and a copper catalyst.⁴⁷     

Correction: Direct electrodeposition of cationic pillar[6]arene-modified graphene oxide composite films and their host–guest inclusions for enhanced electrochemical performance

Correction for ‘Direct electrodeposition of cationic pillar[6]arene-modified graphene oxide composite films and their host–guest inclusions for enhanced electrochemical performance’ by Qunpeng Duan et al., RSC Adv., 2020, 10, 21954–21962, DOI: 10.1039/D0RA03138K.

The authors regret omitting a citation of their related paper published in Frontiers in Chemistry: ‘Facile one-step electrodeposition preparation of cationic pillar[6]arene-modified graphene films on glassy carbon electrodes for enhanced electrochemical performance’ (DOI: 10.3389/fchem.2020.00430) shown as ref. 1 here. The citation should appear as ref. 58 in the original article.¹The authors regret that it was not clear in the original article that the ErGO-CP6/GCE film had been previously reported by them in their related Frontiers in Chemistry paper¹ and therefore the sentence at the start of paragraph 3 on page 2 ‘In this work, we report for the first time preparation of CP6 functionalized graphene films on glassy carbon electrode (GCE) directly from GO-CP6 dispersions by facile one-step pulsed electrodeposition technique (Scheme 1).’ should be ‘In this work, we report the preparation of CP6 functionalized graphene films on glassy carbon electrode (GCE) directly from GO-CP6 dispersions by facile one-step pulsed electrodeposition technique (Scheme 1), which was previously reported by us.⁵⁸’.The authors also wish to clarify the differences between this RSC Advances paper and the Frontiers in Chemistry paper.¹ The papers use different guests molecules and different optimum pulse electrodeposition parameters and the RSC Advances paper reports an improvement in electrochemical performance with additional characterisation, stability studies and the analysis of real samples which are not reported in the Frontiers in Chemistry paper.¹The appropriate figure captions have been updated to reflect the data reproduced from the Frontiers in Chemistry paper.¹Scheme 1 Schematic illustration for the pulsed electrodeposition preparation of ErGO and ErGO-CP6 films on the surface of GCE and sensing the guest molecules by an electrochemical strategy. Reproduced with permission from ref. 1. Copyright 2020 Frontiers.Fig. 1 Characterization of materials. FTIR spectra (A), UV-vis absorption spectra (B), TGA curves of CP6, GO-CP6, and GO (C), and XPS survey spectra of GO and GO-CP6 (D). The data in (a, c and d) have been reproduced with permission from ref. 1. Copyright 2020 Frontiers.Fig. 4 (A) Raman spectra of GO and ErGO. (B) Raman spectra of GOCP6 and ErGO-CP6. Reproduced with permission from ref. 1. Copyright 2020 Frontiers.     

Nanozyme-based catalytic theranostics

Nanozymes, a type of nanomaterial with intrinsic enzyme-like activities, have emerged as a promising tool for disease theranostics. As a type of artificial enzyme mimic, nanozymes can overcome the shortcomings of natural enzymes, including high cost, low stability, and difficulty in storage when they are used in disease diagnosis. Moreover, the multi-enzymatic activity of nanozymes can regulate the level of reactive oxygen species (ROS) in various cells. For example, superoxide dismutase (SOD) and catalase (CAT) activity can be used to scavenge ROS, and peroxidase (POD) and oxidase (OXD) activity can be used to generate ROS. In this review, we summarize recent progress on the strategies and applications of nanozyme-based disease theranostics. In addition, we address the opportunities and challenges of nanozyme-based catalytic theranostics in the near future.

With its diverse physical–chemical properties and highly efficient enzyme-like activities, nanozymes have been widely used in various theranostics.

A nanozyme is a type of nanomaterial (1–100 nm) with enzyme-like activities.^1,2 It can catalyze the reaction of enzyme substrates under physiological conditions, and it has similar catalytic efficiency and enzymatic abilities to natural enzymes. Our previous work found that Fe₃O₄ nanoparticles (NPs) possess an intrinsic peroxidase (POD)-like activity.³ Since then, numerous nanomaterials have been discovered to have POD-, catalase (CAT)-, superoxide dismutase (SOD)-, or oxidase (OXD)-like catalytic activities.⁴ A nanozyme may have more than one type of catalytic activity.⁵ Nowadays, more than 540 nanozymes from 49 elements have been reported from 350 laboratories in 30 countries.^6,7 Among these, iron oxide nanoparticles,⁸ CeO₂,⁹ graphene oxide,¹⁰ carbon nanozymes¹¹ and gold nanoparticles¹² are widely studied and applied.Nanozymes can simulate the catalytic processes of natural enzymes and regulate the redox level of cells, especially on reactive oxygen species (ROS). ROS are intermediate products which emerge in the process of oxygen metabolism, mainly including superoxide anion (O₂˙⁻), hydroxyl radical (·OH), and hydrogen peroxide (H₂O₂).¹³ An abnormal rise in ROS level will destroy the homeostasis of redox in vivo and cause oxidative stress. Nanozymes typically exhibit multiple enzymatic activities. On the one hand, the catalase and superoxide dismutase activity of nanozymes are mainly used to regulate the intracellular ROS level, which plays an important role in protecting cells. On the other hand, the oxidase and peroxidase activity of nanozymes induce ROS production and promote apoptosis, such as in cancer cells.With advantages such as high catalytic efficiency, high stability, biosafety, low cost and easy preparation,¹⁴ nanozymes have been widely used in industrial, medical, and biological fields and in environmental remediation.^2,15,16 Currently, a variety of nanozyme-based biomedical applications have been extensively explored, including biosensors,¹⁷in vitro texts,¹⁸ and antimicrobial¹⁹ and disease treatments, such as cancer therapy, bone marrow therapy and wound healing.²⁰ Here, we summarize the biomedical applications of nanozymes in vivo, as well as addressing the opportunities and challenges of nanozyme-based catalytic disease theranostics in the near future.     

Synthesis of β-alkoxy-N-protected phenethylamines via one-pot copper-catalyzed aziridination and ring opening

A regioselective, copper-catalyzed, one-pot aminoalkoxylation of styrenes using primary and secondary alcohols and three different iminoiodanes as alkoxy and nitrogen sources respectively, is reported. The β-alkoxy-N-protected phenethylamines obtained were used to synthesise β-alkoxy-N-benzylphenethylamines which are interesting new compounds that could act as possible neuronal ligands.

An efficient, regioselective and rapid copper-catalyzed one-pot aminoalkoxylation of styrenes has been developed using different alcohols and phenyl iminoiodinanes.

Aziridines are an important class of nitrogen-containing heterocycles that can be found in a number of biologically active compounds¹ and have also been synthesised by several routes.² Aziridines are suitable synthetic scaffolds or intermediates for the synthesis of many kinds of organic compounds through their ring opening by different nucleophiles including cyanide, aromatic and olefinic compounds, hydride, alcohols, thiols, amines, and halogens, affording various 1,2-difunctionalised compounds.³ Among these 1,2-difunctionalised products, vicinal amino ethers have been obtained using different methodologies including inorganic protic or Lewis acids such as BF₃·Et₂O, Sn(OTf)₂, (NH₄)₂Ce(NO₃)₆, ionic liquids, [Ag(COD)₂]PF₆, and also by an aprotic imidazolium zwitterion, an N,N′-dioxide–Mg(OTf)₂ complex, sulphated zirconia, Ag(i), Au(i), phosphomolybdic acid supported on silica gel, montmorillonites and ceric ammonium nitrate, but always using previously isolated aziridines.⁴ In addition, very recently, the aziridination of alkenes with subsequent ring opening using alcohols under continuous flow was reported.⁵ As far as we know, only a small number of one-pot methodologies has been reported using rhodium, iron(ii) phthalocyanine and ruthenium as the catalysts and different nucleophiles to generate N-protected difunctionalised alkenes. However, the number of N-protected β-amino ethers is limited.⁶ N-Protected β-aminophenyl ethers are useful intermediates in the synthesis of substituted indolines,⁷ and the corresponding N-deprotected β-alkoxyphenethylamines have shown some interesting biological activities.⁸ For these reasons, we decided to look for a one-pot aziridination-ring opening process but using inexpensive copper catalysts and combining different styrenes, alcohols and phenyl iminoiodinanes.     

Improved performance and stability of perovskite solar cells with bilayer electron-transporting layers

Zinc oxide nanoparticles (NPs) are very promising in replacing the phenyl-C₆₁-butyric acid methyl ester (PC₆₁BM) as electron-transporting materials due to the high carrier mobilities, superior stability, low cost and solution processability at low temperatures. The perovskite/ZnO NPs heterojunction has also demonstrated much better stability than perovskite/PC₆₁BM, however it shows lower power conversion efficiency (PCE) compared to the state-of-art devices based on perovskite/PCBM heterojunction. Here, we demonstrated that the insufficient charge transfer from methylammonium lead iodide (MAPbI₃) to ZnO NPs and significant interface trap-states lead to the poor performance and severe hysteresis of PSC with MAPbI₃/ZnO NPs heterojunction. When PC₆₁BM/ZnO NPs bilayer electron transporting layers (ETLs) were used with a device structure of ITO/poly(bis(4-phenyl)(2,4,6-trimethylphenyl)amine) (PTAA)/MAPbI₃/PC₆₁BM/ZnO NPs/Al, which can combine the advantages of efficient charge transfer from MAPbI₃ to PC₆₁BM and excellent blocking ability of ZnO NPs against oxygen, water and electrodes, highly efficient PSCs with PCE as high as 17.2% can be achieved with decent stability.

Perovskite solar cells with PC₆₁BM/ZnO nanoparticles bilayer electron-transporting layers were achieved with a power conversion efficiency of 17.2% and decent stability.

Organic–inorganic hybrid perovskite solar cells (PSCs) have recently attracted tremendous attention because of their excellent photovoltaic efficiencies.^1–4 Since the initial results published in 2009 with efficiencies about 4% using a typical dye-sensitized solar cell structure with liquid electrolyte,⁵ significant progress has been made in device performance through developing high quality film processing methods,^6–10 tuning the perovskite composition,^11–15 optimizing the device architectures^16,17 and synthesizing new hole/electron transport materials.^18–21 Recently, a certified record power conversion efficiency (PCE) of 22.7% was achieved.²² Despite of the success in obtaining dramatically improved PCE, there are certain concerns about the stability and cost towards commercialization. For the state-of-the-art PSCs, perovskites are susceptible to degradation in moisture and air, thus the charge transport materials should prevent the perovskite from exposure to such environments.^20,23–25 One the other hand, PSCs also suffer from the high cost of widely used organic charge transport materials such as 2,2,7,7-tetrakis(N,N-di-p-methoxyphenylamine)-9,9-spirobifluorene (spiro-OMeTAD), phenyl-C_61/71-butyric acid methyl ester (PC_61/71BM).^3,18,26 As alternatives, inorganic materials such as CuSCN,²⁷ CuI,²⁸ CuGaO₂,²⁰ and NiO_x ^29,30 which can be acted as hole transport materials and ZnO,^31,32 SnO₂ ^12,33,34 and TiO₂ ^10,35 which can be acted as electron transport materials are widely studied. Among them, metal oxide nanoparticles (NPs) are very promising in replacing the organic counterparts due to the high carrier mobilities, superior stability, low cost and solution processability at low temperatures.^16,31,33The perovskite/ZnO NPs heterojunction has been demonstrated much better stability than perovskite/PCBM,²³ however it shows lower PCE compared to the state-of-art devices based on perovskite/PCBM heterojunction.^36–38 Thus in this paper, we systematically studied the charge transfer and recombination at CH₃NH₃PbI₃ (MAPbI₃) and ZnO NPs or PC₆₁BM interfaces and tried to fabricate devices with high PCE and super stability simultaneously. We demonstrated that insufficient charge transfer from MAPbI₃ to ZnO NPs and significant interface trap-states lead to the poor performance and severe hysteresis of PSCs based on MAPbI₃/ZnO NPs heterojunction, while the devices based on MAPbI₃/PC₆₁BM show high PCE and negligible hysteresis due to the efficient charge transfer from MAPbI₃ to PC₆₁BM and less recombination at the interface. On the other hand, the MAPbI₃/ZnO NPs devices show excellent stability in air because of the excellent capping ability of ZnO NPs while the stability of MAPbI₃/PC₆₁BM devices is very poor. Thus, we fabricated the PSCs with bilayer electron-transporting layers (ETLs) with the device structure of ITO/poly(bis(4-phenyl)(2,4,6-trimethylphenyl)amine) (PTAA)/MAPbI₃/PC₆₁BM/ZnO NPs/Al, trying to combine the advantages of efficient charge extraction ability of PC₆₁BM and excellent blocking ability of ZnO NPs against oxygen, water and electrode, and finally device with PCE as high as 17.2% was achieved with decent stability.     

Effects of the halogenido ligands on the Kumada-coupling catalytic activity of [Ni{tBuN(PPh2)2-κ2P}X2], X = Cl,Br, I,complexes

Novel nickel(ii) complexes bearing (^tbutyl)bis(diphenylphosphanyl)amine and different halogenido ligands, [Ni(P,P)X₂] = [Ni{^tBuN(PPh₂)₂-κ²P}X₂], (X = Cl, Br, I) are prepared, characterized by IR and NMR spectroscopy, mass spectrometry and X-ray crystallography, and tested as catalysts in the Kumada cross-coupling reaction of model substituted iodobenzenes and p-tolylmagnesium bromide. The data obtained together with DFT calculations indicate that these new catalysts operate in the Ni(i)–Ni(iii) mode. The highest catalytic activity and selectivity are exhibited by [Ni(P,P)Cl₂], which is most easily reduced by the used Grignard reagent to the Ni(i) state. This process is much more energy demanding in the case of the bromido and iodido complexes, causing the appearance of the induction period. [Ni(P,P)Cl₂] is also very active in the cross-couplings of substrates with iodine atoms sterically shielded by ortho substituents. The data obtained are in good accordance with the described positive effect of the increased electron-releasing power of N-substituents R′ on the overall catalytic performance of [Ni{R′N(PPh₂)₂-κ²P}X₂] complexes.

Novel nickel(ii) complexes [Ni(P,P)X₂] = [Ni{^tBuN(PPh₂)₂-κ²P}X₂], X = Cl, Br, I, are prepared, characterized by IR and NMR spectroscopy, mass spectrometry and X-ray crystallography, and tested as catalysts in the Kumada cross-coupling reaction.

In recent years, the chemical and catalytic properties of transition metal complexes bearing N-functionalized bis(diphenylphosphanyl)amine ligands, R′N(PPh₂)₂, have been under consideration.^1,2 For instance, chromium complexes with this type of ligand are known to oligomerize various olefins.^3–8 In addition, a large number of [M{R′N(PPh₂)₂-κ²P}X₂] complexes, M = Ni, Pd, Pt; X = Cl, Br, I (see Scheme 1), exhibiting small P–M–P bite angles, were recently reviewed.² Selected palladium(ii) complexes bearing X = Cl,^9–14 Br,^14,15 I,^14,16 catalyze the Suzuki–Miyaura and Heck coupling reactions. Some structurally characterized Ni(ii) analogous complexes bearing X = Cl,^17–28 Br,^18,29–37 I,^18,36,38 catalyze polymerization of norbornene^20,21 or oligomerization (X = Br,^32,34 I,³⁸) and polymerization (X = Br²⁹) of ethene. It should be stressed that nickel(ii) complexes of this family are only moderately active catalysts in the Suzuki–Miyaura reaction.³⁵ On the other hand, they exhibit a considerable catalytic activity and acceptable selectivity in the Kumada coupling reaction.^23,35Open in a separate windowScheme 1General structure of the studied complexes [M(P,P)X₂], M = Ni, Pd, Pt; X = Cl, Br, I; R'' = ((S)-CHMePh), (CH₂)₃Si(OCH₃)₃, ^tBu.Kumada coupling is one of the most important C–C coupling reactions³⁹ for a wide range of purposes, including pharmaceutical applications.⁴⁰ Although palladium-based complexes are mostly the first choice catalysts for this coupling,^41–43 complexes of other transition metals such as iron,^44,45 and nickel^46,47 are also used. We have already investigated the catalytic activity of [Ni{R′N(PPh₂)₂-κ²P}X₂], R′ = (S)-CHMePh; X = Cl, Br,³⁵ and R′ = (CH₂)₃Si(OMe)₃; X = Cl,²³ in homogeneous systems to extend the scope of nickel(ii) catalysts in this reaction. The latter catalyst has also been anchored onto mesoporous molecular sieves, thus providing an active heterogenized catalyst.²³ In homogeneous catalytic reactions, both catalysts bearing R′ = (S)-CHMePh) showed a substrate conversion (68% for X = Cl and 63% for X = Br),³⁵ significantly lower compared to that of the catalyst with R′ = (CH₂)₃Si(OMe)₃ and X = Cl (79%).²³ These results suggested that the increased electronegativity of coordinated halogenido ligands and the increased electron-donating power of the R′ moiety have positive effects on the catalytic efficiency of this type of nickel(ii) complexes. In the work presented herein, the effects exerted by the identity of halogenido ligands X⁻ and the R′ moiety on catalytic activity and selectivity were further assessed by exploring three novel complexes, [Ni{^tBuN(PPh₂)₂-κ²P}X₂], X = Cl, Br, I, henceforth referred to as [Ni(P,P)X₂], bearing the strongly electron-releasing ^tbutyl (^tBu) group as R′.     

Synthesis of 3-selanylbenzo[b]furans promoted by SelectFluor®

A simple and practical protocol for the synthesis of 3-selanyl-benzo[b]furans mediated by the SelectFluor® reagent was developed. This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans via a metal-free procedure under mild conditions. The intramolecular cyclization reaction was carried out employing an electrophilic selenium species generated in situ through the reaction between SelectFluor® and organic diselenides. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy, and its reactivity was explored.

This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans mediate by Selectfluor® reagent. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy.

The benzo[b]furan scaffold is an important structural motif that is present in natural products and in synthetic compounds with therapeutic proprieties.¹ Substituted benzo[b]furans have shown a broad range of biological activities,² being found in a variety of pharmaceutical targets, such as Viibryd® and Ancoron® (Fig. 1).³ These drugs are used for treatment of depression and for cardiac arrhythmias, respectively. An efficient method to obtain substituted benzo[b]furans is the intramolecular cyclization reaction between 2-alkynylphenol or 2-alkynylanisole derivatives with different electrophilic species to generate a wide variety of 3-substituted-benzo[b]furans. This strategy is especially useful because of the atom-economic synthesis under mild conditions.⁴Open in a separate windowFig. 1Substituted benzo[b]furans in commercial drugs.Organoselenium compounds have attracted great interest due the large number of biological applications and their versatile reactivity.⁵ From a synthetic point of view, the ease cleavage of the Se–Se bond in diselenide compounds can generate species with different reactivity, as radical, electrophile, and nucleophile. This ample usefulness becomes the diselenides in key synthetic intermediates to introduce selenium moiety in organic compounds or to catalyse organic transformations.^5,6Despite the recent advances in the synthesis of 3-selanyl-benzo[b]furans, new electrophiles and reactional conditions were explored (Scheme 1).^{7–9,11–15} Initially, the establishing work by Larock and co-workers toward the synthesis of 3-selanyl-benzo[b]furans through the intramolecular cyclization of 2-(phenylethynyl)anisole with PhSeCl in CH₂Cl₂ at room temperature.⁷ In 2009, Zeni and co-workers demonstrated the synthesis of 3-selanyl-benzo[b]furans employing PhSeBr as an active electrophile.⁸ A pioneering protocol was reported by Zeni and co-workers, which employed FeCl₃ (1.0 equiv.) and diorganyl diselenides in CH₂Cl₂ at 45 °C.⁹ Additionally, Lewis acids have been used as effective catalysts in Se–Se bonding cleavage to access functionalized selenium compounds.¹⁰ Afterward, alternative methods were developed, such as the synthesis of 3-selanyl-benzo[b]furans mediated by PdCl₂/I₂, I₂/water, and CuI (1.5 equiv.).^11–14 More recently, Liu and co-workers reported a radical cyclization reaction using selenium powder as selenium source and AgNO₃ as catalyst in DMSO at 100 °C.¹⁵Open in a separate windowScheme 1Methodologies to prepare 3-selanyl-benzo[b]furans.Although, there are different methodologies to prepare 3-selanyl-benzo[b]furans and other functionalized selenium compounds through the reaction between diselenides compounds with oxidant reagents or Lewis acids, alternative electrophilic selenium species should be employed to avoid metals and/or toxic reagents.^9–15 Furthermore, RSeCl and RSeBr,^7,8 obtained from the reaction of diselenides with SO₂Cl₂ (or Cl₂) and Br₂ respectively, are commercially available and largely used as selenylating agent. However, these species present a low stability under moisture, and the high nucleophilicity of chloride and bromide leaving groups can lead to undesirable side reactions.On the other hand, SelectFluor® is a versatile reagent used for different applications, such as fluorination reactions,¹⁶ C–H functionalization¹⁷ and organic function transfer.¹⁸ In addition, SelectFluor® has been used as an efficient method for intramolecular annulation reactions, due its higher reactivity.¹⁹ This ample application together with the desirable characteristics of the SelectFluor®, such as the higher stability, non-hydroscopic solid and hazard-free source of fluorine,²⁰ promoted new possibilities to investigate fluorine chemistry. In 2004, Poleschner and Seppelt prepared PhSeF derivatives by the reaction between diorganyl diselenides and XeF₂ in CH₂Cl₂ as a solvent at −40 °C.²¹ The products were characterized by low-temperature ¹⁹F and ⁷⁷Se NMR, and it was the first confirmation of this type of electrophilic selenium compound. Although electrophilic selenium catalysis (ESC) with electrophilic fluoride reagents as oxidants has been demonstrated in the functionalization of alkenes,²² fewer knowledge about the reactivity of this selenium electrophilic species is available in the literature.²³Based on the development of new electrophilic selenium reagents,^9–14,24 herein, we describe a metal-free synthesis of 3-selanyl-benzo[b]furans under mild conditions using this very reactive electrophilic selenium species (RSe-F), generated in situ at room temperature by the reaction of diorganyl diselenides with SelectFluor® reagent (Scheme 1). Moreover, the higher reactivity of RSe-F species could be explored for the insertion of selenium moiety in other building blocks because the environmentally friendly reactional condition, and the replacing chlorine and bromine by the non-nucleophilic fluorine counter ion, can partially circumvented some side reactions.     

Photoelectrochemical photocurrent switching effect on a pristine anodized Ti/TiO2 system as a platform for chemical logic devices

We report here the effect of the photoelectrochemical photocurrent switching (PEPS) observed on highly-ordered pristine anodized Ti/TiO₂ for the first time. At negative potential bias, blue irradiation gives cathodic photocurrent, whereas anodic photocurrent was observed for ultraviolet irradiation. We believe this phenomenon is due to the electron pathway provided by Ti³⁺ defect states.

We report here the effect of the photoelectrochemical photocurrent switching (PEPS) observed on highly-ordered pristine anodized Ti/TiO₂ for the first time.

Titanium dioxide, being one of the most studied materials, still draws much attention from researchers.^1,2 It is considered to be a very promising material due to its high chemical stability, nontoxicity, and its unique properties. Due to stable and robust photoactivity, titania is widely used in the design of solar cells³ and photocatalytic applications.⁴ In addition to the fact that titanium dioxide occurs in several crystalline modifications, it can also be obtained in various forms, such as, for example, nanotubes,⁵ nanofibers,⁶ and nanosheets.⁷ The photocatalytic performance of TiO₂ is highly dependent on crystallinity,⁸ phase content, form, and preparation method.⁹ It was reported that highly ordered arrays of TiO₂ nanotubes are characterized by short charge transport distance and little carrier transport loss.⁵ Therefore, electrochemically fabricated TiO₂ nanotube arrays are preferable compared to random non-oriented titania.¹⁰ Great varieties of photoelectrochemical behaviour can be achieved by doping¹¹ and surface modification.^12,13An interesting feature has recently been demonstrated for highly ordered arrays of TiO₂ nanotubes obtained by double stepwise electrochemical anodization of a titanium foil (Ti/TiO₂). Together with our colleagues observed that localized illumination of Ti/TiO₂ surface in water solution triggers proton flux from irradiated area.¹⁴ The photocatalytic activity of TiO₂ is based on photogenerated electron–hole pairs. Under the electric field of Ti/TiO₂ Schottky junction and due to upward surface band bending, efficient spatial charge separation occurs, and photoexcited holes (h⁺) reach TiO₂ – solution interface. The h⁺, which is a strong oxidizing agent, can react with water, and a pronounced pH gradient arises due to water photolysis. Thus, titanium dioxide can be used to trigger local ion fluxes, and proton release is associated with anodic photocurrent. The use of the light-pH coupling effect to control pH-sensitive soft matter was previously demonstrated.^15,16 Complementary species, H⁺ and OH⁻, annihilating when occurring simultaneously, extend chemical arithmetic with subtraction operation opening way to pure chemical calculations.¹⁷ Ion fluxes consideration as information transducers in solution were proposed¹⁸ and performing simple logic operations was demonstrated.¹⁹ This phenomenon opens perspectives to biomimetic information processing and developing effective human–machine interfaces.²⁰Photoelectrodes using light and potential as inputs and yielding photocurrents are being considered as the basis for logic devices. In this way, optical computing compatible with existing silicon-based devices may be performed.Logic operations are described by Boolean algebra operating with truth values denoted 0 (false) and 1 (true). Elementary logical operations are modelled by logic gates producing single binary output from multiple binary inputs and physically implemented by some switch. As for photoelectrode based information processing, the photoelectrochemical photocurrent switching (PEPS) effect is utilized. This effect is that under appropriate external polarization or/and illumination by light with appropriate photon energy, switching between anodic and cathodic photocurrent may be observed for n-type semiconductors and the opposite for p-type.^21,22Without further modification, this effect was observed for a very limited number of materials, such as bismuth orthovanadate, lead molybdate, V–VI–VII semiconductors, and some others. To show this effect, the majority of semiconductors require electronic structure perturbation creating new electron pathways. A convenient solution is specific modifier adsorption onto the semiconductors'' surface, providing a sufficient level of electronic coupling. Photoelectrodes made of nanocrystalline TiO₂ modified by cyanoferrate,^13,23 and ruthenium²⁴ complexes, thiamine, folic acid,²⁵ and carminic acid²⁶ demonstrated PEPS behavior.Surprisingly, we observed the PEPS effect on non-modified Ti/TiO₂ obtained by anodation of Ti plates.Highly ordered arrays of anatase Ti/TiO₂ were obtained. Crystallinity was proved by XRD (Fig. S1a^†). Fig. 1a shows a SEM image of TiO₂ nanotube arrays obtained as described above. According to SEM image, an average pore diameter is ca. 60 nm. As reported, highly ordered TiO₂ nanotubes possess a short charge transport distance and little carrier transport loss. Therefore, highly ordered TiO₂ nanotube arrays fabricated by electrochemical anodization of titanium may exhibit some enhanced capacity of electron transfer than non-oriented ones of random mixture.¹⁰Open in a separate windowFig. 1(a) SEM image of the TiO₂ nanotubes array. The inset shows cross-section view. (b) Scheme of a cell for photocurrent measurements experiment, CE – counter electrode, RE – reference electrode, WE – working electrode.According to Mott–Schottky analysis, at potential bias more positive than −0,697 V vs. Ag/AgCl reference electrode upwards band bending occurs (Fig. S2^†). Heat treatment in a nonoxidizing atmosphere leads to Ti³⁺ formation. Appearance of Ti³⁺ self-doping was proved by EDX analysis (Fig. S1b^†). It was previously reported that Ti³⁺ introduces gap states which act as recombination centers and pathways for electron transfer.^27–29 Ti³⁺ species in reduced TiO₂ introduce a gap state between valence and conduction bands.^27,28We studied dependence of photocurrent on applied potential. Ultraviolet irradiation (365 nm) gave positive photocurrent for all potentials studied in range from −0.6 V to 0.6 V vs. Ag/AgCl reference electrode (Fig. S3^†). The photocurrent increases as the potential becomes more positive, but eventually saturates. The dependence of the current on the potential under blue irradiation (405 nm) had a different character. Sigmoid function with inflection point at 0–0.2 V was observed for blue light.It should be noticed that photocurrent plotted against time on Fig. 2–4 as well as against potential on Fig. S3^† is ΔI = I_{under illumination} − I_{in darkness}. Steady state current values were used for calculations.Open in a separate windowFig. 2Photocurrent curves under chopped irradiation by (a) 365 nm UV LED, (c) 405 nm blue LED at applied potential bias +300 mV vs. Ag/AgCl, and corresponding scheme of electron pathway at +300 mV polarization under irradiation by (b) 365 nm UV LED and (d) 405 nm blue LED.Open in a separate windowFig. 3Photocurrent curves under chopped irradiation by (a) 365 nm UV LED, (c) 405 nm blue LED at applied potential bias −300 mV vs. Ag/AgCl, and corresponding scheme of electron pathway at −300 mV polarization under irradiation by (b) 365 nm UV LED and (d) 405 nm blue LED.Open in a separate windowFig. 4(a) XOR logic realized on negatively polarized (−0.3 V) pristine Ti/TiO₂ by two source irradiation, input A – UV light (365 nm), input B – blue light (405 nm); blue light gives anodic photocurrent, UV – cathodic photocurrent. The current, significantly different from the dark one, is taken as output 1, otherwise – 0. When irradiated by blue and UV light simultaneously, anodic and cathodic current compensate each other, and no total photocurrent observed. Thus output 0, when both inputs are 1 (b) OR logic realized on positively polarized (+0.3 V) non-modified Ti/TiO₂ by two sources of irradiation. Irradiation by any of them, blue or UV, gives anodic photocurrent.At +300 mV vs. Ag/AgCl irradiation by both blue and ultraviolet light give anodic photocurrent (Fig. 2a and c). The UV-irradiation (λ = 365 nm, 5 mW cm⁻²) excites electron directly to the conduction band (CB) of TiO_2, which is further transferred to conducting titanium support (Fig. 2b). When Ti/TiO₂ electrode in thermodynamic equilibrium with electrolyte, an upward surface band bending occurs at the semiconductor–liquid junction. This phenomenon obstructs electron injection from the conduction band into the electrolyte and forces electron drift to conducting substrate. The fast and steady photocurrent production/extinction upon light on/off indicates efficient charge separation and low recombination.Blue light (λ = 405 nm, 70 mW cm⁻²) is characterized by lower energy than UV-irradiation, which is not sufficient to excite the electron to CB. But electron excited by blue light can be trapped by Ti³⁺ located close to the conduction band and transferred to conduction support from these levels (Fig. 2c). An initial current spike following by an exponential decrease suggesting a fast recombination process. It should be also noticed than when irradiation is switched off photocurrent ‘overshoots’ as the remaining surface holes continue to recombine with electrons.At more negative potential (−300 mV vs. Ag/AgCl, for example) applied to non-modified anodized Ti/TiO₂ photoelectrode, we observed anodic photocurrent during irradiation by UV light (Fig. 3a) whereas blue irradiation gave anodic photocurrent (Fig. 3c). Excitation within bandgap by UV-irradiation leads to cathodic photocurrent (Fig. 3b). In the case of irradiation by blue light, electron trapping by Ti³⁺ occurs in the same manner as at +300 mV polarization. But at negative polarization, the energy landscape is such that electron transport to electron donor in solution is preferable (Fig. 3d). As a result, cathodic current occurs.Thereby, photoelectrode activity of non-modified anodized Ti/TiO₂ can be switched from anodic to cathodic and vice versa by applying various potentials and various photon energies. This is the effect of photoelectrochemical photocurrent switching.Thereby, when Ti/TiO₂ is irradiated simultaneously by blue and UV light being negatively polarized, competition between cathodic and anodic photocurrents occurs. Returning to Boolean logic, the PEPS effect allows us to perform annihilation of two input signals and implement optoelectronic XOR logic gate. XOR logic operation outputs true (1) only when input values are different and yield zero otherwise.It is necessary to assign logic values to input and output signals to analyse the system based on Ti/TiO₂ PEPS effect in terms of Boolean logic. Logical 0 and 1 are assigned to off and on states of the LEDs, respectively. Different wavelengths (365 and 405 nm) correspond to two different inputs of the logic gate. In the same way, we can assign logic 0 to the state when photocurrent is not generated and logic 1 to any nonzero photocurrent intensity irrespectively on its polarization (cathodic or anodic). Fig. 4 demonstrates how different types of Boolean logic are realized by irradiation of Ti/TiO₂. Light sources are denoted here as inputs, UV light – A and blue light – B. If the corresponding light source is switched ON and illuminates photoelectrode Ti/TiO₂, this input is ‘1’, otherwise, it''s ‘0’. The photocurrent is read as output. It''s considered to be ‘1’ if significantly differs from dark value and ‘0’ otherwise.At −300 mV vs. Ag/AgCl, pulsed irradiation with UV diode (365 nm, 5 mW cm⁻²) results in anodic photocurrent, which is consistent with electron excitation to CB and transfer to conducting support. Irradiation with blue LED (405 nm) gives cathodic photocurrent due to electron capture by Ti³⁺ states following by transferring to electron acceptor in solution. Simultaneous irradiation with two LEDs with adjusted intensity yields zero net current as anodic and cathodic photocurrents compensate effectively (Fig. 4a).At positive potentials, pulsed irradiation with UV diode gives anodic photocurrent pulses, as well as the blue one. It is interesting to note that when two sources of light are simultaneously irradiated, the photocurrents created by each of them individually do not summarize. At +300 mV, photocurrent output under the influence of two light inputs (365 nm and 405 nm) follows OR logic giving positive output if at least one of inputs is positive (Fig. 4b). Fig. 5 demonstrates the reconfigurable logic system which characteristics can be changed via an appropriate polarization of the photoelectrode regarded as programming input. Two irradiation sources are considered as inputs. OR/XOR logic is realized depending on programming input.Open in a separate windowFig. 5A reconfigurable logic system based on non-modified Ti/TiO₂. Light sources are inputs. The choice between XOR and OR function is determined by programming input of potential bias. At +300 mV OR logic is realized, at −300 – XOR logic. Corresponding truth table is presented.In summary, PEPS effect on modified nanocrystalline TiO₂ was previously discussed a lot.^13,23–26 In this work we report the same phenomenon for pristine anodized Ti/TiO₂ system. Due to substructure of Ti/TiO₂ system, it shows characteristic response to various range of illumination, including visible range and polarization. The Ti/TiO₂ system is a simple and robust model of chemical logic gates. Suggested mimicking of logic functions in aqueous solutions allows further integration of element into communication with living objects¹⁶vs. intrinsically associated photooxidation and degradation, but rather activation for needed function.³⁰     

Organocatalytic sulfa-Michael/aldol cascade: constructing functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter

A practical sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylates has been developed, which allows efficient access to functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter in moderate to good yields with high enantioselectivities.

A sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylate has been developed, which allows access to 2,5-dihydrothiophenes bearing a quaternary carbon center in moderate to good yields with high enantioselectivities.

Among the various classes of heterocycles, members of the thiophene family have received particular attention from the chemical community because of their widespread occurrence as ubiquitous motifs in natural products, pharmaceuticals, agrochemicals as well as materials.¹ In this context, the 2,5-dihydrothiophene ring is a common structural feature of many bioactive compounds and a potential intermediate for various synthetic applications.² Over the decades, only a few examples of the assembly of optically active 2,5-dihydrothiophenes have been documented.³ For instance, the Spino^3b group successfully prepared non-racemic dihydrothiophenes using an efficient chiral auxiliary. The first gold-catalyzed cycloisomerization of α-hydroxyallenes to 2,5-dihydrothiophenes was reported by Krause^3c and co-workers. Then in 2010, the Xu^3e group developed a highly stereoselective domino thia-Michael/aldol reaction between 1,4-dithiane-2,5-diol and α,β-unsaturated aldehyde catalyzed by a chiral diphenylprolino TMS ether, which provided a new avenue for the synthesis of functionalized 2,5-dihydrothiophenes.Quaternary carbon stereocenters are often contained in natural products and pharmaceuticals.⁴ Compared with the chiral pool synthesis,⁵ the procedure of chiral materials or catalysts to construct such sterically congested stereogenic centers is more challenging because of the difficulty of orbital overlap.⁶ To date, a lot of progresses have been made in the construction of chiral quaternary carbon centers in cyclic compounds,⁷ which are greatly accelerated by the advancement of transition metal catalysis,⁸ and organocatalysis,⁹ including methods beyond radical initiation.¹⁰ However, only few examples are about the construction of a quaternary carbon in 2,5-dihydrothiophene ring.¹¹ Inspired by the previous work of the Xu group,^3e we describe herein an elegant organocatalytic asymmetric cascade sulfa-Michael/aldol reaction, providing a convenient way for the synthesis of 2,5-dihydrothiophenes bearing a chiral quaternary cabon center.     

Retraction: Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signaling pathway in IL-1β-induced osteoarthritis chondrocytes

Retraction of ‘Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signalling pathway in IL-1β-induced osteoarthritis chondrocytes’ by Bin Zhu et al., RSC Adv., 2018, 8, 36422–36429, DOI: 10.1039/C8RA02418A.

The Royal Society of Chemistry hereby wholly retracts this RSC Advances article due to concerns with the reliability of the data.The images in the article were screened by an image integrity expert who confirmed that some of the western blots images in this paper had been duplicated in other articles. There are no common authors between the papers.The Col II band in Fig. 3B of this paper has been duplicated as the p62 band in Fig. 4A of ref. 1.One of the blots in the control band (GAPDH) in Fig. 3D has also been reused as a blot in Fig. 2C of ref. 1 and in Fig. 4A of ref. 2.The authors were asked to provide the raw data for this article but did not respond. Given the significance of the concerns about the validity of the data, and the lack of raw data, the findings presented in this paper are not reliable.The authors have been informed but have not responded to any correspondence regarding the retraction.Signed: Laura Fisher, Executive Editor, RSC AdvancesDate: 7^th January 2021     

Preparation of solution processed photodetectors comprised of two-dimensional tin(ii) sulfide nanosheet thin films assembled via the Langmuir–Blodgett method

We report the manufacture of fully solution processed photodetectors based on two-dimensional tin(ii) sulfide assembled via the Langmuir–Blodgett method. The method we propose can coat a variety of substrates including paper, Si/SiO₂ and flexible polymer allowing for a potentially wide range of applications in future optoelectronic devices.

Norton et al. report the manufacture of fully solution processed photodetectors based on two-dimensional tin(ii) sulfide assembled via the Langmuir–Blodgett method.

Two-dimensional (2D) materials are condensed matter solids formed of crystalline atomic layers held together via weak van der Waals forces.¹ They have a wide range of applications including use as channel materials in transistors,² absorber layers in solar cells,³ light emission,⁴ energy storage⁵ and drug delivery⁶ among others. 2D materials often have different properties from their bulk counterparts such as increased strength⁷ and electrical conductivity.⁸ 2D semiconductors may exhibit a change in electronic states from confinement in 1D.⁹ Thin films are often required for the creation of devices from nanomaterials for practical applications and can often be made into flexible devices such as thin film solar cells¹⁰ or photodetectors.^11,12 Thin film solar cells in particular have several advantages over conventional solar cells including lower materials consumption and are lightweight, yet have the potential for high power conversion efficiency.¹⁰Many of the two-dimensional materials produced thus far have been derived from mechanical exfoliation, where Scotch tape or an equivalent is manually used to remove single crystalline layers from a bulk van der Waals solid followed by transfer to a substrate. Whilst this method in general produces extremely high quality crystalline atomic layers,¹³ and is therefore often used to produce prototype devices, it inherently lacks scalabilty. In order to address the problem of mass manufacture of two dimensional materials, liquid phase exfoliation (LPE) was introduced as a cost effective method for producing two dimensional nanomaterials¹⁴ with the possibility of 100 L scales being produced and production rates up to 5.3 g h⁻¹ demonstrated by Coleman et al. with both NMP and aqueous surfactant solutions utilised.¹⁵ This method also does not require the high temperatures needed for methods such as CVD¹⁶ or transfer between the growth and final substrates. Liquid phase exfoliated nanomaterials are also directly processable from solution.¹⁵ Furthermore, LPE has been shown to be effective for the production of a wide range of 2D materials such as graphene,¹⁵ transition metal dichalcogenides¹⁷ and monochalcogenides such as SnSe.¹⁸Tin(ii) sulfide (SnS) is a van der Waals solid with a puckered ab structure consisting of alternating Sn and S atoms, and is isostructural and isoelectronic with black phosphorus.¹⁹ The bulk material has attracted interest due to its indirect band gap energy of 1.07 eV,²⁰ similar to bulk silicon at 1.14 eV. This band gap energy for SnS is useful for applications such as photodetection²¹ and due to its higher theoretical Shockley–Queisser efficiency limit (24%) for solar cells.²² The liquid phase exfoliation method established by Coleman et al. enables nanosheets to be separated from the bulk into solution utilising matching surface energies of the material and solvent.²³ Liquid phase exfoliation of SnS was first reported by Lewis et al. it was established that as layer number reduced, band gap energy increased, and by tuning layer number the onset of photon absorption can be tuned over the near infrared²³ to visible range.²⁴ Overall, LPE is capable of creating large quantities of nanosheets, with potential for industrial scale production. Liquid phase exfoliated SnS has, for example, recently been used in the creation of photoelectrochemical systems with strong stability under both acidic and alkali conditions.²⁵ Many of the functional devices produced thus far have been derived from micromechanical exfoliation and manual nanomanipulation. A far more elegant solution to producing functional devices is to assemble them from solution, for example Kelly et al. recently reported a transistor based on exfoliated WSe₂ nanosheets.²The Langmuir–Blodgett method involves the use of a trough with a layer of water and controllable barriers to compress the film. Nanomaterials in solution are added to the surface of the water and spread evenly to reduce their surface energy,²⁶ often by using a low surface tension spreading solvent such as chloroform.²⁷ The surface pressure is measured as the film is compressed with the substrate being withdrawn when the film becomes solid.²⁸ The Langmuir–Blodgett method has the advantages of large area deposition and improved control of the film at the nanoscale in comparison to vacuum filtration as well as the advantage of requiring no volatile solvents in comparison to liquid–liquid assembly methods. The use of movable barriers also allows for greater film compression.²⁶This method has been used to assemble large scale films of exfoliated MoS₂ by Zhang et al. MoS₂ was exfoliated using n-butyl lithium followed by solvent exchange. MoS₂ was deposited onto the water surface using a 1 : 1 mix of DMF and dichloroethane. Substrates up to 130 cm² were coated with a surface coverage of 85–95%.²⁶ Collapse mechanisms of MoS₂ Langmuir films have also been studied²⁹ alongside MoS₂ deposition on the surface of water with an upper hexane layer.³⁰ Graphene films have also been prepared using the Langmuir–Blodgett method.³¹ The Langmuir–Blodgett method has been used for the assembly of organo-clay hybrid films via the coating of octadecylammonium chloride in a 4 : 1 chloroform : ethanol solution onto a 2D nanoclay liquid phase exfoliated film using an electrospray method.³² A solvent mix of chloroform and NMP has also been utilised for the deposition of nanosheet films.³³ Recently the Langmuir–Blodget method has been used for the assembly of unmodified clay nanosheets,³⁴ Ti₃C₂Tx MXene nanosheet films for the removal of Cr(vi) and methyl orange from an aqueous environment³⁵ as well as for the growth of rGO wrapped nanostructures for use in electrocatalysts.³⁶Given the chemical similarity of the basal planes of inorganic 2D materials, we hypothesised that the assembly of group IV–VI nanomaterials such as SnS should also be possible at the air water interface. Due to their interesting semiconducting and properties described, it should also be possible to produce prototype optoelectronic devices from a fully solution processed pathway. In this paper we now communicate a methodology to assemble thin films comprised of 2D SnS nanosheets using the Langmuir–Blodgett technique (Scheme 1a). We report the use of these films in simple photodetectors. This represents a scalable methodology to produce fully solution processed devices based on 2D materials.Open in a separate windowScheme 1Preparation of SnS nanosheet thin films via the Langmuir–Blodgett method. (a) Cartoon of Langmuir–Blodgett film preparation. (b) Image of Langmuir–Blodgett trough with compressed SnS film. (c) Surface pressure profile during film compression. (d) Image of sample prepared on Si/SiO₂ substrate with edges masked (scale bar 1.5 cm). Scheme 1(a) shows the step by step process of film preparation. Firstly, bulk SnS is broken down by liquid phase exfoliation from the bulk material to produce a stable dispersion of crystalline nanosheets. Characterisation of the exfoliated nanomaterials was undertaken using atomic force and electron microscopy yielding average sheet dimensions of 23.9 nm height × 224 nm longest side length (Fig. S1^†). The nanosheets were then deposited onto the water air interface. The film is then compressed whilst an immersed substrate is withdrawn, leading to the creation of a densely packed nanosheet film. Scheme 1(b) shows that SnS can be successfully deposited on the water–air interface via the addition of chloroform as a spreading solvent, as shown previously with other Langmuir based films.²⁷Scheme 1(a) shows a z-type deposition of SnS as the hydrophilic glass and Si with a 300 nm oxide layer is withdrawn through the film at 1 atm pressure. The film compression occurred at a rate of 5.88 cm² s⁻¹. No further treatments were performed to change the hydrophilicity of the substrates, the oxide layer present was sufficient to provide hydrophilicity to the substrate.³⁷Scheme 1(c) shows a gradual increase in surface pressure as the area was decreased from 1175 cm² to 298 cm² before a sharp increase in pressure, indicating the film has reached full compression. The sharp increase in surface pressure during compression is common in Langmuir–Blodgett assembled films of nanomaterials.³⁸ In response to compression the surface pressure profile in Scheme 1(c) rises rapidly until it reaches a maximum due to the size of the sheets and the potential difficulty in sliding over each other compared to polymers or smaller nanomaterials. Scheme 1(d) shows that the film is capable of being coated onto Si/SiO₂ with a mask defining the areas covered.We characterised the resulting structural and electronic properties of the thin film of SnS nanosheets deposited via the Langmuir–Blodgett method using a range of techniques. Fig. 1(a) shows a height profile AFM image of a film edge with an average on-film roughness (R_a) of 31.9 nm and an average film thickness of 78.6 nm (Fig S3^† provides an additional film profile). Previous work on Langmuir–Blodgett deposition has produced thinner films. The use of high centrifugation speeds yielded 7 nm thick films for a single deposition³¹ whilst the use of lithium ion intercalation before exfoliation enabled film thicknesses of under 2 nm per layer to be realised.²⁶ The average film thickness is above the average sheet thickness, suggesting that the film is made up of overlapping flake multilayers. However, the thickness of the films is significantly lower than those grown via chemical bath deposition (e.g. 290 nm (ref. 39)) indicating that thinner films can be produced compared to chemical bath methods, and potentially at a much lower cost than methods such as CVD. Images of the film morphology in plan view SEM (Fig. 1(b)) suggest no notable alignment of the nanosheets in the lateral dimension as the film is formed and deposited (see Fig S4^† for statistical analysis of sheet angle measurement). The coverage of the film is 94.6% as determined by image thresholding using imagej software to determine the area left uncovered. This gives a coverage of 0.0142 gm⁻² as calculated from average thickness, SnS density and % coverage of the substrate. Preliminary SEM results also suggest that the Langmuir–Blodgett method is effective at coating SnS onto a variety of substrates including polyolefin films (Parafilm®), aluminium foil and paper (Fig S6^†). We also probed the structure of the thin films by powder X-ray diffraction (XRD). After exfoliation and film assembly, the diffraction peak associated with the (400) of SnS is still the most intense reflection but is characterised by a much larger FWHM compared to that of bulk SnS under the same recording conditions (0.442° ± 18.5% compared to 0.175° ± 5%). This indicates a successful breakdown of the crystal structure and thinning of the material in the (400) plane during exfoliation due to the reduction in long range order⁴⁰ (reflections for bulk SnS are assigned to orthorhombic SnS and indexed in Fig S2^†). The lack of any additional peaks indicates that there has not been any significant degradation of the material to the corresponding oxide which is in agreement with previous works.^24,25 The reflections at 88° and 94° are unlikely to be from crystalline silicon⁴¹ due to the thick oxide layer and low angle of incidence used. We tentatively ascribe these peaks to the 3,0,−3 and 3,2,4 peaks for SnS.⁴¹ However a confident assignment of this reflection requires further studies.Open in a separate windowFig. 1Structural characterisation of SnS nanosheet thin films assembled by the Langmuir-Bllodgett method. (a) AFM image of LB assembled SnS film edge. Inset film profile, scale bar = 10 μm. (b) SEM image of LB assembled film on Si/SiO₂ at 3 kV using secondary electron imaging, scale bar = 1 μm. (c) XRD pattern of coated film and bulk SnS powder, (additional peaks labelled in Fig. S2^†). (d) Raman spectra and for bulk and Langmuir–Blodgett assembled SnS nanosheets. (e) UV-Vis spectra of SnS suspension and deposited SnS film on glass (f) Tauc plot of SnS solution and film.We also characterised the optical properties of the nanosheet thin films using Raman and UV-Vis-NIR absorption spectroscopy. No shifts in the Raman peak positions B₃g, Ag and B₃u from bulk SnS to Langmuir–Blodgett film were observed. The broad feature at around 300 cm⁻¹ for the LB film may potentially be due to SnS₂ and Sn₂S₃ impurities.⁴² It is predicted that due to the lower density compared to SnS⁴³ the impurities may increase in concentration compared to the bulk after centrifugation. These impurities may have significant effects on the efficiency of the devices produced.⁴⁴A shift in peak positions is typically observed in nanomaterials which exhibit quantum confinement,⁴⁵ this occurs at 14 nm for SnS.⁴⁶Fig. 1(e) shows a UV-Vis spectra from which the absorption coefficients at fixed wavelengths may be obtained, for 350 nm, 405 nm, 450 nm, 500 nm, 600 nm and 800 nm the values obtained were: 2.26 × 10⁵ cm⁻¹, 2.21 × 10⁵ cm⁻¹, 2.16 × 10⁵ cm⁻¹, 2.04 × 10⁵ cm⁻¹, 1.67 × 10⁵ cm⁻¹ and 1.05 × 10⁵ cm⁻¹ respectively, this matches well to the absorption coefficients of SnS in literature (greater than 10⁴ cm⁻¹).⁴⁷ It also suggests there may be a greater response at shorter wavelengths. Fig. 1(f) shows a band gap of 0.92 eV for the exfoliated SnS in NMP which is below the expected value of 1.07 eV (ref. 20) although lies within the reasonable error introduced by the use of Tauc plots.⁴⁸ The band gap also matches well with SnS exfoliated in NMP in previous work.²⁴ The band gap of the film appears to change from nanosheet suspension to film in 1(f). This has been observed previously for Langmuir–Blodgett⁴⁹ and other deposited films. It has also been observed that apparent decreases in band gap may occur due to the presence of scattering artefacts within films of nanoscale objects.⁵⁰We then produced simple prototype photodetectors via the printing of Ag nanoparticles to form interdigitated electrodes on top of the SnS nanosheet film. Additionally, SnS films were deposited onto lithographically defined Au interdigitated electrodes for characterisation and referencing to the printed devices.Previously SnS photodetectors have been created via methods such as electron beam deposition,⁵¹ thermal evaporation⁵² and chemical bath deposition.⁵³ The Langmuir–Blodgett method allows SnS to be directly processed into a film from a liquid phase exfoliated solution, allowing them to be produced cheaply and with the potential for scalability.Inset to Fig. 2(a) is an image of an interdigitated Ag electrode SnS photodetector device with an area of 6.4 × 10⁻⁵ m². The electrodes can be clearly identified with an average spacing of 99 μm, and an average RMS edge roughness value of 1.89 μm (determined for individual contact lines using the imageJ ‘analyze_stripes’ plugin⁵⁴ (Fig S7^†)). Fig. 2(a) shows an increase in the slope of the I–V curve in the third quadrant indicating a reduction in resistance under 1 sun illumination (1000 W m⁻²) with the AM1.5 spectrum. No short circuit current under illumination was observed indicating that the device functions as a photoconductor. The non-linear response upon negative biasing is due to initial trap filling which once equilibrium has been reached results in linear device operation. Previously it has been shown that silver diffusion into SnS has an interstitial doping effect, neutralising defect states and lowering the film resistivity.^55,56 It is also possible that the Ag ink morphology and the concentration of nanoparticles in the ink may play an effect on the device properties.⁵⁷ A resistivity of 2.85 × 10⁶ Ω sq⁻¹ was obtained for the device which is significantly higher than SnS films prepared by physical vapour deposition (250 Ω sq⁻¹),⁵⁸ likely due to poor carrier mobility between flakes.Open in a separate windowFig. 2(a) IV curves of printed contacts SnS device under darkness and AM1.5 illumination with inset photograph of pseudo Langmuir–Blodgett device with printed Ag contacts scale bar 5 mm. (b) Device under +40 V bias under fixed darkness/illumination cycle. Fig. 2(b) indicates that a clear response is present under illumination when an external bias is applied (giving a field strength of 0.4 V μm⁻¹). Closer inspection shows a fast and slow decay component following the illumination being blocked. This biexponential decay indicates the capture of trapped carriers and the presence of trap states within the device.^59,60 This again supports the photoconductive nature of the device operation with a rise time of ∼0.22 s and a fall time of ∼2.83 s,⁶¹ both being longer than the shutter closing/opening time of 3.7 ms (which was considered negligible). The rise time is the time taken to get from 10% to 90% of the light current with the fall time being the time taken from 90% of the light current to 10%.Previous work performed by Jiang et al. has shown a slow fall time in Ag/SnS photoconductor devices arising from carrier trapping.⁶² Similarly, in our devices the large rise time may also be due to the presence of a high trap density which must be filled upon light exposure.The mean dark current is 2.78 × 10⁻¹⁰ A with a standard deviation of 2.02 × 10⁻¹¹ A. The mean light current was found to be 3.92 × 10⁻¹⁰ A with a standard deviation of 4.03 × 10⁻¹¹ A. A poor signal to noise ratio appears to be present within the device, possibly due to the large number of SnS nanosheets involved in charge carrier transit, leading to a low signal, hence a low signal to noise ratio. The noise could be reduced via surface passivation⁶³ or the use of a diode like structure to reduce leakage current under reverse bias.⁶⁴ A low responsivity of 2.00 × 10⁻⁹ A W⁻¹ ± 1.5 × 10⁻¹⁰ A W⁻¹ was found for energies above the band gap energy of 0.6 eV for the deposited film.The low responsivity may be due to poor bridging between individual SnS nanosheets and the poor transport of holes between adjacent flakes (hopping) relative to the higher mobility within each flake.⁶⁵ There are potentially hundreds of nanosheets between the contacts as determined by the average length obtained (Fig S1^†). To confirm that the optical response was due to the presence of the SnS a reference device was tested (without SnS deposition, Fig S8^†) with no photoresponse observed. Despite the low responsivity, it is notable that the SnS devices fabricated are one of the few examples of a thin film photodetector device based on 2D materials requiring only solution processing at ambient temperature and atmospheric pressure.To demonstrate that the observed behaviour originates from the photoresponse of the SnS flakes a second device was fabricated by pseudo Langmuir–Blodgett deposition on to lithographically defined Au interdigitated electrodes (15 μm separation) on fused silica (inset Fig. 3(b)). This enabled us to remove any effect of photoinduced Ag migration from the observed behaviour as well as eliminating the issue of potential printing irregularities. Fig. 3(a) shows that the devices display a similar photoresponse to the devices with printed Ag electrodes when exposed to modulated AM1.5 illumination. The dark current remains similar at ∼0.3 nA, though during illumination the current is higher (0.7 nA vs. 0.4 nA). This increase directly correlates to the higher electric field strength (0.66 V μm⁻¹vs. 0.4 V μm⁻¹) between the interdigitated electrodes. The responsivity of the device was determined to be 1.79 × 10⁻⁸ A W⁻¹, with a photoresponse rise and fall time of 0.77 s and 0.85 s respectively. The responsivity is lower than for photodetectors prepared by Guo et al.⁶⁶ Improvements to the device to improve the responsivity could include methods to improve the lateral size of nanosheets such as intercalation.⁶⁷ Other routes to improve the device may include doping^68,69 or a change in architecture to a phototransistor type device.⁷⁰ The removal of potential SnS₂ and Sn₂S₃ impurities via methods such as annealing at 500 °C, 500 mbar pressure under argon or the use of higher quality starting material may also be a key route to improve the efficiency of the device.⁴²Open in a separate windowFig. 3(a) Device under 30 s off, 30 s on solar simulator illumination at 1 sun and 10 V bias (b) IV curves under darkness and 350 nm illumination with inset optical microscopy image of contacts (c) monochromatic illumination responses under 10 V bias mapped onto UV-Vis transmission spectra (d) device response under fixed 10 V bias under 350 nm and 405 nm monochromatic illumination.It is also noticeable that the level of noise present in Fig. 3(a) is reduced compared to that in Fig. 2(b), indicating that the Ag electrodes themselves (in addition to the SnS sheets) also affect the performance.When exciting using AM1.5 illumination it is possible that thermal effects may be present which could give rise to the observed behaviour.In order to demonstrate a true photoresponse monochromatic illumination was used to determine if illumination energies above the band gap generated a photocurrent response in the device. Fig. 3(b) shows a small response under 350 nm (3.54 eV) illumination. (IV curves for other wavelengths are available in Fig. S9^†). Fig. 3(c) shows an increased response for 350 nm wavelength as determined via the IV curves. This increased response is likely due to increased absorption as shown in the UV-Vis spectra (Fig. 1e), the signal at longer wavelengths is difficult to observe due to the low responsivity. A higher response at lower wavelength has been observed previously for SnS.⁵³ Fig. 3(d) shows that an increase in current is present under 350 nm and 405 nm illumination which can be cycled on and off. A rise and fall time of 1.09 of 1.44 seconds respectively was observed for 405 nm illumination. A light/dark current ratio of 1.03 was obtained under 405 nm. To account for noise the on and off section had their current averaged using origin software. A drift in current during measurement was observed, this was considered as the reason for the significant difference between the dark current for 350 nm and 405 nm. To further reduce noise surface passivation may also be used to improve the device properties.⁶³ Alternatively, an increase in bias voltage or an increase in monochromatic illumination intensity may improve the signal: noise ratio though may risk damage to the device. A magnified off/on cycle for 405 nm is shown in Fig. S10.^†In conclusion, we report here a methodology for the assembly of 2D SnS nanosheets into thin films using the Langmuir–Blodgett method, and the testing of the films as prototype all-solution processed photodetectors. Tin(ii) sulfide was successfully exfoliated with an average sheet thickness of 33 nm with the average longest side length of 224 nm. A nanosheet based film was coated onto a variety of substrates via the Langmuir–Blodgett method with the addition of chloroform as a spreading solvent. The films were found to be polycrystalline with an average thickness of 78.6 nm with a high surface coverage up to 94.6% for an Si/SiO₂ substrate. The films were found to be semiconductive with the ability to respond to light under bias as shown by AM1.5 and monochromatic illumination. Proof-of-concept photodetectors have been successfully produced. It was also confirmed that the response was due to the photoresponse as opposed to a heating effect. This deposition method could potentially be used to create a variety of SnS films using different exfoliated nanosheet sizes separated via cascade centrifugation as well as the potential for future flexible photodetector devices. Despite the low responsivity, large rise and fall times further work could allow the gain to be optimised. We also note that the use of the Langmuir–Blodgett trough is an easily scalable technology and could provide coatings over very large area substrates not only for photodetectors but for other devices such as thin film solar cells.     

Hyperpolarization study on remdesivir with its biological reaction monitoring via signal amplification by reversible exchange

Our experiments indicate hyperpolarized proton signals in the entire structure of remdesivir are obtained due to a long-distance polarization transfer by para-hydrogen. SABRE-based biological real-time reaction monitoring, by using a protein enzyme under mild conditions is carried out. It represents the first successful para-hydrogen based hyperpolarization application in biological reaction monitoring.

Hyperpolarized proton signals in the entire structure of remdesivir are obtained due to a long-distance polarization transfer by para-hydrogen. Biological real-time reaction monitoring, by using a protein enzyme under mild conditions is carried out.

Nuclear magnetic resonance is a versatile and powerful analytical method for real-time monitoring of significant bio-catalyzed reactions. However, even though NMR has great potential as a reaction monitoring system, providing much structural information, it has not been studied in depth due to low sensitivity. To enhance the sensitivity, the hyperpolarization technique has been suggested which has long been acknowledged as a breakthrough in reaction monitoring by NMR.There are major hyperpolarization techniques, generating non-Boltzmann population distribution for hyperpolarized signal to noise such as dynamic nuclear polarization,^1–5 spin-exchange optical pumping,^6–8para-hydrogen induced polarization (PHIP),^9–11 and signal amplification by reversible exchange (SABRE).^12–14 In the case of para-hydrogen-based SABRE, the substrate and the para-hydrogen bind to a catalyzing metal complex together, thus allowing polarization to be transferred to the substrate through scalar coupling. To achieve better enhancement, the iridium N-heterocyclic carbene complex¹⁵ exhibits the highest polarization transfer efficiency, which delivering an 8100-fold enhancement in ¹H NMR signal amplification relative to non-hyperpolarized pyridine. Additionally, enhancements can be increased by employing the bulky electron-donating phosphines of the Crabtree catalyst.¹⁶ Most iridium N-heterocyclic carbene catalysts are produced as [Ir(H)₂(NHC)(substrate)₃]Cl while they are capable of delivering various NMR signal gains such as ¹H,^17–1913C,^9,20,2115N,^22–2419F,^25,2631P.²⁷ Recently, a published work has described the extension of the SABRE substrate scope to include a wide range of common drugs such as tuberculosis drugs,²⁸ antifungal,²⁹ and antibiotic agents.^30,31 It is mainly N-heterocyclic compounds with low molecular weight. Hyperpolarization experiments using large molecular weight COVID-19 drug candidates have rarely been reported.³² Here, we extend the current scope of biologically relevant SABRE substrates to remdesivir and monitor its enzymatic hydrolysis.SABRE has been widely considered as a potentially promising reaction monitoring tool for the real-time reaction via hyperpolarization.^33,34 After its successful application on the amide-coupling reaction monitoring, it could not be applied to the biological reaction monitoring due to the solvent used for the reaction, mild biological reaction conditions, and mostly, small molecule polarization capacity. Therefore, its direct application on the biological reaction could open up new possibilities in the real-time reaction monitoring via hyperpolarization.To overcome this COVID-19 pandemic, many researchers have engaged in drug development including drug repurposing. Recently, remdesivir has received emergency use authorization from the FDA, as the first organic medicine to treat COVID-19 around the world. Its prodrug form has been controversial as its intact form is not detectable even after two hours post-injection and as its efficiency for all clinical treatment should also be catalyzed by several key biological reactions including esterase hydrolysis reaction.^35–37 Therefore, further research on its molecular level of understanding is still required for enhanced drug development. Along with that, repurposing nucleoside analogue drugs have been considered as the attractive future drug candidates to overcome this pandemic and beyond. They target the RNA polymerase and prevent viral RNA synthesis in a broad spectrum of RNA viruses, including human coronaviruses.^38,39 Thus, to develop the most appropriate repurposing nucleoside analogue drug candidates for COVID-19, in-depth timely research on its pharmacokinetics and pharmacodynamics at the molecular level is also essential to overcome this pandemic and its consequent recurrences.In our previous study, we reported the hyperpolarization on the several anti-viral drug candidates of COVID-19.³² However, these drug candidates have been reported rather ineffective in treating COVID-19.⁴⁰ Furthermore, even though those unprecedented hyperpolarization on the large drug molecules are new, their polarizations are only done in methanol solvent, which is not applicable in a biological form.³² Our research results indicate successful hyperpolarization of remdesivir via SABRE under mild conditions and hyperpolarization performed in DMSO, a more non-toxic solvent for in vitro application. To provide a more clinical perspective of using this technique, its biological reaction by enzyme was successfully monitored by signal enhancement via SABRE. Moreover, to widen its future applications, we added one more Ir-catalyst by matching external magnetic field condition for efficient polarization transfer to remdesivir. Our findings will expand newly applicable research areas, not only in biological reaction monitoring via NMR, but also in other biomedicine research, in order to cope with dreadful diseases in the future.Remdesivir structure has several potential key polarization sources for SABRE: nitrile, amine, and triazine. However, its complex structure and large molecular weight have been considered as the limiting factors for hyperpolarization. Fig. 1 depicts the normal signal and its hyperpolarized signal after SABRE using IMes-Ir-catalyst, which shows the different extent of hyperpolarization of remdesivir. Among the amplified proton signals, proton 6 represents the highest hyperpolarization attached to the 5′-carbon of the nucleoside. However, its polarization indicates no major difference compared to those protons in the whole structure.Open in a separate windowFig. 1Remdesivir molecular structure and its normal ¹H NMR signal in the methanol-d₄ solvent (black spectrum). Hyperpolarized signals from remdesivir after SABRE in the presence of 130 G external magnetic field in the methanol-d₄ solvent (red spectrum).Therefore, we can anticipate its polarization transfer is mostly from the SABRE-Relay^41–43 or SPINOE,^44–46 which are discussed more on conclusion. To optimize hyperpolarization, the external magnetic field is changed, and its polarization is maximized at around 130 G.However, no major difference was noted in the extent of hyperpolarization in different magnetic fields, which could have been due to Ir-catalyst''s fast exchange. Furthermore, its polarization transfer could be from other factors such as SPINOE, other than from the Zeeman effect and J-coupling matching condition. Referring to a recent study on the SABRE hyperpolarization difference between Ir-catalysts,⁴⁷ we tested the SABRE with Crabtree''s-Ir-catalyst, which indicates the different polarization number. Interestingly, its polarization confirmed that the number of hyperpolarization using the Crabtree''s-Ir-catalyst was slightly higher than IMes-Ir-catalyst. The hyperpolarization patterns in the different magnetic field also present no major changes from the different Ir-catalyst (Fig. 2 and S1^† for structures of Ir-catalysts). Remdesivir is considered to be one of the most important treatments amid this pandemic due to its usage in blocking viral RNA production, leading to an additional study on hyperpolarization in which a more biological solvent has been conducted. Interestingly, SABRE in the CD₃SOCD₃ with IMes-Ir-catalyst shows the highest polarization efficiency with approximately 17-fold enhanced signal (Fig. 3). DMSO has various biological impacts, such as the ability to increase the skin penetration of chemicals. It can pass through biological membranes, including human skin, probably by changing lipid packing structure and producing breaks in the bilayer.^48,49 This result observed in the current research opens a new possibility for applying the in vitro experiment with biological tests since DMSO has been widely used in the in vitro drug test.^50,51 Its polarization result of remdesivir among the Ir-catalyst led to higher IMes-Ir-catalyst than Crabtree''s-Ir-catalyst, different from the CD₃OD. This indicates the polarization transfer mechanism with chelating structure is not solely dependent on the solvent or catalyst. Furthermore, the polarization trend in its structure is the highest in the proton of 9, followed by the proton of 5, which bonded with 5′-carbon of the nucleoside. This different trend in each Ir-catalyst indicates that the polarization transfer efficiency varies depending on solvents in different external magnetic fields and different solvent systems.Open in a separate windowFig. 2Signal amplification value (SE) of individual protons from hyperpolarized remdesivir using IMes-Ir-catalyst and Crabree''s-Ir-catalyst.Open in a separate windowFig. 3(a) ¹H spectrum of remdesivir before (black spectrum) and after SABRE (red spectrum) in the DMSO-d₆; (b) signal amplification value (SE) of individual protons from hyperpolarized remdesivir using IMes-Ir-catalyst and Crabtree''s-Ir-catalyst.Remdesivir activates analogue, inhibits RNA-dependent RNA polymerase, and prevents viral RNA synthesis as a phosphoramidate prodrug.⁵² The activation pathway of remdesivir has been proposed to have four steps: (1) cell entrance; (2) enzymatic elimination of masking group with 2-ethylbutyl ester and phenoxy; (3) phosphorylation; and (4) incorporation into COVID-19 RNA.⁵³ The masking group of remdesivir performs increasing hydrophobicity to facilitate cellular entry.⁵⁴ Also its inventor found that the proton of 7 was shifted to 3 to 4 ppm when the masking group of remdesivir was removed.^55,56 Monitoring hydrolysis of a 2-ethylbutyl ester by esterase confirmed the proton of 7* in 3.2 ppm via hyperpolarization (Fig. 4a). The splitting pattern of 7* is controversial because of its doublet instead of quartet. It attributes to several factors. Because of the 5-membered ring intermediate from remdesivir, the splitting pattern of 7* could be affected. The initial metabolism of remdesivir produces an intermediate of cyclopentane containing 7* is made.⁵⁷ Therefore, stereochemical relations in the equilibrium among protons in 5-membered rings cannot be determined by simply measuring coupling constants, except in cases where the substitution pattern of the specific ring system has been carefully investigated. It could be covered by a water peak close to 7*. Another possibility is that hyperpolarized proton 8 of the 2-ethyl butyl group that is released by enzymatic hydrolysis can be observed. However, the cleavage of the phenoxy group is hard to prove via spectra due to little variation in the signal of aromatic region (Fig. S2^†). Its normal cleaved remdesivir signal after the same reaction time and condition was not shown in a scan and its maximum polarization was calculated by ∼22 enhancement after comparing with the multiple scan average (Fig. 4b and S3^†). To the best of our knowledge, this is the first study that conducts hyperpolarization reaction monitoring via SABRE in biological condition is conducted for the first time. Furthermore, its NMR-based reaction monitoring on a biologically important prodrug suggests that significantly wide applications in biomedical research. Its application can be significantly widened in the biomedical researches.Open in a separate windowFig. 4(a) ¹H spectra of enzymatic hydrolysis monitoring of remdesivir; elimination of 2-ethylbutyl ester group; (b) ¹H spectra of remdesivir; enzymatic hydrolysis after 120 min (black spectrum) and amplified through hyperpolarization (red spectrum) at the same time.